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SYSTEMATIC REVIEW
published: 07 September 2021
doi: 10.3389/fsufs.2021.685801
Frontiers in Sustainable Food Systems | www.frontiersin.org 1September 2021 | Volume 5 | Article 685801
Edited by:
Everlon Cid Rigobelo,
São Paulo State University, Brazil
Reviewed by:
Eveline M. Ibeagha-Awemu,
Agriculture and Agri-Food Canada
(AAFC), Canada
Maura Santos Reis De Andrade Da
Silva,
Universidade Estadual de São
Paulo, Brazil
*Correspondence:
Sarah N. Evanega
snd2@cornell.edu
Specialty section:
This article was submitted to
Crop Biology and Sustainability,
a section of the journal
Frontiers in Sustainable Food Systems
Received: 17 May 2021
Accepted: 28 July 2021
Published: 07 September 2021
Citation:
Karavolias NG, Horner W, Abugu MN
and Evanega SN (2021) Application of
Gene Editing for Climate Change in
Agriculture.
Front. Sustain. Food Syst. 5:685801.
doi: 10.3389/fsufs.2021.685801
Application of Gene Editing for
Climate Change in Agriculture
Nicholas G. Karavolias 1,2 , Wilson Horner 1,3 , Modesta N. Abugu 4,5 and Sarah N. Evanega 5
*
1Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA, United States, 2Innovative Genomics Institute,
University of California, Berkeley, Berkeley, CA, United States, 3Plant Gene Expression Center, US Department of
Agriculture-Agricultural Research Service, University of California, Berkeley, Albany, CA, United States, 4Horticultural
Sciences Department, University of Florida, Gainesville, FL, United States, 5Department of Global Development, Cornell
University, Ithaca, NY, United States
Climate change imposes a severe threat to agricultural systems, food security, and
human nutrition. Meanwhile, efforts in crop and livestock gene editing have been
undertaken to improve performance across a range of traits. Many of the targeted
phenotypes include attributes that could be beneficial for climate change adaptation.
Here, we present examples of emerging gene editing applications and research initiatives
that are aimed at the improvement of crops and livestock in response to climate change,
and discuss technical limitations and opportunities therein. While only few applications of
gene editing have been translated to agricultural production thus far, numerous studies
in research settings have demonstrated the potential for potent applications to address
climate change in the near future.
Keywords: gene edited crops, livestock genetics, climate change, agriculture, food system, food security,livestock
genetic resources, crop biotechnology
INTRODUCTION
Climate change poses a severe threat to the future of the environment as it pertains to agriculture,
biodiversity, human society, and nearly every facet of our world. The primary cause of climate
change is the anthropogenic addition of greenhouse gases to the atmosphere. Due to these human
emissions, the average temperature of the planet has risen by nearly 1◦C since 1850 (IPCC, 2018;
Nunez et al., 2019). Even if warming were to be halted at 1.5◦C, which would require drastic and
immediate global action, long-term effects of past emissions would linger for centuries or millennia
(IPCC, 2018). The magnitude of the effects depends on the amount of emissions; in general, more
frequent heatwaves, droughts, floods, and persistent sea level rise and global temperature increases
are expected (IPCC, 2018). Indeed, many of these effects are already being observed (IPCC, 2018;
Nunez et al., 2019; Shukla et al., in press).
In both natural ecosystems and agricultural settings, plants and animals are being forced to
contend with novel conditions that change more quickly than their pace of adaptation. Rising
temperatures and shifting precipitation regimes will drastically alter the biological landscape,
resulting in species migration, invasion, and extinction (Urban, 2015; Nunez et al., 2019). One
meta-review of more than 130 studies has estimated that one in six species may go extinct due to
the changing climate (Urban, 2015). Simultaneously, global food supplies are declining as droughts
and floods impact agricultural output. Under a range of warming scenarios, agricultural output is
expected to decline globally. Productivity of major commodity crops will be affected, especially in
lower latitudes where the effects of climate change on yield will be more severe (Shukla et al., in
press).
Karavolias et al. Gene Editing Agriculture Climate Change
In response to these challenges, the use of gene editing,
also referred to as genome editing or genome engineering, has
emerged as a method to either aid in the adaptation of organisms
to climate change or help mitigate the effects of climate change
on agriculture.
Gene editing is a method to generate DNA modifications
at precise genomic locations. These modifications can result
in knockout or knockdown of one or multiple genes without
the permanent insertion of any foreign DNA. Alternatively,
genes from within the organism’s genepool or from other
organisms can be inserted into precise locations within the
genome to knock-in a new trait. Transcription activator-
like effector nucleases (TALENs), Zinc Finger Nucleases
(ZFNs), and CRISPR/Cas systems have all been utilized to
achieve precise gene edits (Gaj et al., 2016; Khalil, 2020).
The precision and efficiency of generating edits has been
tremendously improved by the introduction of CRISPR/Cas
systems, although there is certainly still a role for other
gene editing technologies. The application of gene editing
techniques has generated great potential for developing crops
and livestock that can better manage the impositions of
climate change.
We seek here to illuminate the ways in which gene editing
may help combat the deleterious effects of climate change by
highlighting current efforts to apply these techniques in crops
and livestock. We will summarize the efforts undertaken thus
far and describe the limitations and opportunities that exist with
gene editing technologies. Tables 1–4, provided at the end of the
review, summarizes the breadth of applications of gene editing in
crops and livestock.
Climate Change Will Inhibit Agricultural
Productivity
The effects of climate change have already started to emerge
and will undoubtedly worsen. Currently, crops in lower latitude
regions have begun to experience yield declines, while higher-
latitude regions have experienced an increase in yield (Iizumi
et al., 2018; Shukla et al., in press). However, global declines in
yield and crop suitability are projected over the course of the
century as a direct result of climate change. According to the
Intergovernmental Panel on Climate Change (IPCC), extreme
weather events will disrupt and decrease global food supply
and drive higher food prices (Shukla et al., in press). In dry
areas of the planet especially, climate change and desertification
are likely to reduce agricultural productivity. Areas closer to
the equator will be most vulnerable to declines in crop yield
as temperature increases, with the continents of Asia and
Africa having the largest populations vulnerable to increased
desertification. Indeed, desertification has already started to
reduce agricultural productivity and biodiversity, compounded
by unsustainable land management and increased population
pressure. While it is unclear to what extent aridity will increase
on a global scale, it is likely that the area at risk of salinization
will increase. Climate change will also contribute to current land
degradation with increased droughts, floods, rising seas, and
more intense tropical storms (Shukla et al., in press).
Effects of Climate Change on Crops
The major contributing greenhouse gas to climate change is
carbon dioxide (CO2) (IPCC, 2018; Shukla et al., in press),
which generally has a positive effect on plant growth. As CO2
concentration increases, so too does the rate of photosynthesis
and carbon assimilation (an effect known as CO2fertilization)
(Wang et al., 2020). Simultaneously, however, the nutritional
quality of food decreases in response to heightened CO2(Shukla
et al., in press). Furthermore, the increased growth associated
with higher CO2may be offset by other environmental factors;
there has been an observed decline in this CO2fertilization
effect in the past 30 years, likely due to shifting nutrient
concentrations and lower availability of water (Wang et al., 2020).
Given the aforementioned increase in extreme temperature and
precipitation events, combined with the shifting prevalence and
range of diseases across the globe (Fisher et al., 2012; Bett
et al., 2017), the overall effect of climate change on crops will
be detrimental (Iizumi et al., 2018; Shukla et al., in press).
Already, global yields of maize, wheat, and soybeans have slightly
decreased from 1981 to 2010 relative to the pre-industrial climate
(Iizumi et al., 2018).
Effects of Climate Change on Livestock
Livestock will similarly be negatively affected by climate change.
Increasing temperature and shifting precipitation directly impact
livestock themselves, the crops grown for their feed, and diseases
that infect them (Rojas-Downing et al., 2017; Shukla et al.,
in press). Increasing temperatures will have perhaps the most
profound effects on livestock: heat stress impacts feed intake and
can reduce weight gain, decreases reproductive efficiency, has
multiple negative health effects, and increases mortality in many
livestock species (Rojas-Downing et al., 2017).
Climate Change Impacts Biodiversity and
Food Systems
Beyond agriculture, the effects of climate change on biodiversity
are no less severe. A recent meta-review of 97 studies found
that even with only moderate increases of global temperature,
biodiversity will suffer significant declines (Nunez et al.,
2019). The pressures of climate change on biodiversity, in
combination with increased agricultural demand, have also
served to exacerbate the oftentimes antagonistic relationship
between agricultural and natural landscapes. The impact of
individual climate change effects and their intersections are
complex. Broadly, the direct and indirect consequences of climate
change will be deleterious to plant and animal performance in
cultivated systems (Figure 1).
Mitigating the deleterious impacts of climate change on
biodiversity is paramount. However, most applications of gene
editing have converged on agricultural commodities: there are
very few instances of gene editing for climate change in non-
commodity organisms. This review therefore focuses on how
gene editing solutions can address the broad effects of climate
change on agriculture while maintaining the importance of
applying these transformative technologies to the totality of
biodiversity threatened by climate change.
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Karavolias et al. Gene Editing Agriculture Climate Change
TABLE 1 | Summary of gene-editing applications for abiotic stress.
Species Trait category Trait targeted Gene(s) Edited* Method Year published References
Banana Abiotic stress Semi-dwarfed Ma04g15900
Ma06g27710
Ma08g32850
Ma11g10500
Ma11g17210
CRISPR/Cas9 2019 (Shao et al., 2020)
Maize Abiotic stress Drought tolerance ARGOS8 CRISPR/Cas9 2016 (Shi et al., 2017)
Rice Abiotic stress Drought Tolerance EPFL9 CRISPR/Cas9, CRISPR/Cpf1 2017 (Yin et al., 2017)
Rice Abiotic stress Early flowering Hd2, Hd4, Hd5 CRISPR/Cas9 2017 (Li et al., 2017)
Rice Abiotic stress Salt tolerance OsRR22 CRISPR/Cas9 2019 (Zhang A. et al., 2019)
Cattle Abiotic stress Thermotolerance SLICK CRISPR/Cas9 2018 (Bellini, 2018)
APPLICATIONS OF GENE EDITING IN
AGRICULTURE
Here we present an extensive exploration of gene editing-
based solutions in response to the daunting limitations to
agricultural productivity imposed by climate change. We
note that these examples are mostly from public institutions
and represent proof-of-concept experiments rather than
commercialized technologies.
Increasing Abiotic Stress Tolerance
Abiotic stresses, including but not limited to drought, salinity,
and flooding, pose some of the most severe threats to agricultural
productivity in the face of climate change. Abiotic stress is
anticipated to become more severe in agricultural systems as a
result of climate change. Current research efforts demonstrate
that gene editing is an effective tool in broadening resistance of
crop tolerance as described in the following examples (Table 1,
Figure 2).
Salinity Tolerance in Rice
Rice, a staple food for more than half of the world’s population,
is of primary importance for global food security (Chauhan
et al., 2017). Two major abiotic stresses that affect rice are
drought and salinity, necessitating research explorations into
the potential of leveraging gene editing for developing tolerant
varieties. One such exploration was the use of CRISPR/Cas9
to knockout OsRR22, a gene associated with salt susceptibility
in rice (Zhang A. et al., 2019). Rice plant performance in
high salinity environments (0.75% NaCl) was improved with no
concomitant decreases in grain yield, plant biomass, or grain
quality. Edited lines were on average 19% shorter in saline
solution whereas wild type plants were 32% shorter. Edited
plants also had much less severe biomass reductions due to salt
exposure compared to unedited plants, and showed no significant
differences to unedited plants in the absence of saline. Saline
studies were conducted in the greenhouse and overall agronomic
performance was evaluated in the field. Researchers found that
edited plants had much less severe biomass reductions due to salt
exposure compared to wild type plants (Zhang A. et al., 2019).
Drought Tolerance in Rice
Rice has also been engineered to improve drought and
high temperature tolerance by targeting stomatal development.
Stomata, which are anatomical features on the surface of all
crop plant tissues, serve as the major sites of water loss. In this
study researchers targeted a positive regulator of stomatal density
in rice (Yin et al., 2017); while they did not explicitly test the
effects of this editing on water use efficiency, other research
has shown that stomatal reductions in rice have clear, positive
implications for water use efficiency (Caine et al., 2019). Rice lines
with reductions in stomatal densities had better yield in severe
drought and were able to maintain lower temperatures despite
no differences in yield. Stomatal density reductions achieved
by a cisgenic approach in this case mirrored stomatal density
reductions achieved by a knockout-based, gene-editing approach.
Thus, reducing stomatal densities by gene-editing or cisgenic
approaches could enable plants to resist water deficits and could
also increase heat tolerance.
Enabling Northern Production of Rice
An additional editing effort in rice produced early maturing rice
that is more amenable to production in northern latitudes (Li
et al., 2017). Northern latitudes experience longer day lengths
and cooler temperatures. Applications of CRISPR/Cas9 to the
flowering related genes Hd2,4 and 5, generated rice plants that
flowered significantly earlier than their wild-type counterparts,
making them more fit for northern production. These varieties
may be well-suited for use in future conditions where
temperatures and other climatic conditions near equatorial
regions render farmlands less fertile. Early flowering plants may
also be a useful adaptation against water deficit: by shortening the
life span of crops through early flowering, less cumulative water
may be required.
Semi-dwarf Banana Varieties
In banana, gene editing using CRISPR/Cas9 to generate
knockouts of genes for the biosynthesis of gibberellins has
facilitated the development of a semi-dwarfed variety. This
variety may be more resistant to lodging as a result of intense
winds, typhoons, and storms, anticipated to increase in severity
as a result of climate change (Shao et al., 2020). Semi-dwarfed
varieties have historically been an important trait in crop
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Karavolias et al. Gene Editing Agriculture Climate Change
TABLE 2 | Summary of gene-editing applications for disease tolerance.
Species Trait category Trait targeted Gene(s) Edited* Method Year published References
Banana Disease Banana streak virus eBSV CRISPR/Cas9 2019 (Tripathi J. N. et al., 2019)
Barley Disease Broad spectrum MORC1 CRISPR/Cas9 2018 (Kumar et al., 2018)
Cacao Disease Resistance to
phytopthora
TcNPR3 CRISPR/Cas9 2018 (Fister et al., 2018)
Cassava Disease Cassava brown
streak disease
ncbp1/2 CRISPR/Cas9 2019 (Gomez et al., 2019)
Cotton Disease Verticillium dahliae Gh14-3-3d CRISPR/Cas9 2018 (Zhang Z. et al., 2018)
Cucumber Disease Broad spectrum viral
resistance
eIF4e CRISPR/Cas9 2016 (Chandrasekaran et al., 2016)
Grape Disease Powdery mildew VvMLO3 CRISPR/Cas9 2020 (Wan et al., 2020)
Grapefruit Disease Citrus canker CsLOB1 promoter;
CsLOB
CRISPR/Cas9 2016, 2017 (Jia et al., 2016, 2017)
Potato Disease Potato virus Y Coilin C-terminal CRISPR/Cas9 2019 (Makhotenko et al., 2019)
Rice Disease Bacterial blight
resistance
OsSWEET 14 promoter;
OsSWEET11 promoter;
OsSWEET13
CRISPR/Cas9 2013, 2015 (Jiang et al., 2013; Zhou et al.,
2015)
Rice Disease Rice leaf blast
resistance
OsERF922 CRISPR/Cas9 2016 (Wang et al., 2016)
Rice Disease Powdery mildew TaEDR1 CRISPR/Cas9 2017 (Zhang et al., 2017)
Rice Disease Broad spectrum bsr-k1 CRISPR/Cas9 2017,2018 (Kumar et al., 2018; Zhou X.
et al., 2018)
Rice Disease Rice tungro
spherical virus
eIF4G CRISPR/Cas9 2018 (Macovei et al., 2018)
Rice Disease Bacterial blight SWEET11, 13,14
promoters
TALENs 2019 (Xu et al., 2019)
Rice Disease Bacterial blight SWEET11,13,14
promoters
CRISPR/Cas9 2019 (Oliva et al., 2019)
Rice Disease Bacterial blight Os8N3 CRISPR/Cas9 2019 (Kim et al., 2019)
Tomato Disease Broad spectrum SlDMR6 CRISPR/Cas9 2016 (de Toledo Thomazella et al.,
2016)
Tomato Disease Powdery mildew SlMLO1 CRISPR/Cas9 2017 (Nekrasov et al., 2017)
Tomato Disease Tomato yellow leaf
curl virus
Coat and replicase protein
of TYCV
CRISPR/Cas9 2018 (Tashkandi et al., 2018)
Tomato Disease Bacterial speck SlJAZ2 CRISPR/Cas9 2018 (Ortigosa et al., 2019)
Wheat Disease Powdery mildew TaMLOs TALENS, CRISPR/Cas9 2014 (Wang et al., 2014)
Cattle Disease Mastitis Lysostaphin, hLYZ ZFN 2013, 2014 (Liu et al., 2013, 2014)
Cattle Disease Tuberculosis SP110 TALE nickase 2015 (Wu et al., 2015)
Cattle Disease Leukotoxin
resistance
CD18 ZFN 2016 (Shanthalingam et al., 2016)
Cattle Disease Tuberculosis NRAMP1 CRISPR/Cas9 2017 (Gao et al., 2017)
Chicken Disease Avian leukosis chNHE1 CRISPR/Cas9 2020 (Koslov et al., 2020)
Grass Carp Disease Grass carp reovirus gcJAM-A CRISPR/Cas9 2018 (Ma et al., 2018)
Pig Disease Porcine Respiratory
Syndrome Virus,
innate immunity
CD163, CD1D CRISPR/Cas9 2014 (Whitworth et al., 2014)
Pig Disease Porcine respiratory
syndrome virus
CD163 CRISPR/Cas9 2016 (Whitworth et al., 2016)
Pig Disease Porcine respiratory
syndrome virus
CD163 CRISPR/Cas9 2017 (Burkard et al., 2017, 2018)
Pig Disease Classical swine fever shRNA knock-in to
Rosa26 locus
CRISPR/Cas9 2018 (Xie et al., 2018)
Pig Disease, nutrition Classical swine
fever, fat-1
fat-1 knock-in to Rosa26
locus
CRISPR/Cas9 2018 (Li M. et al., 2018)
Pig Disease Transmissible
gastroenteritis virus
ANPEP CRISPR/Cas9 2019 (Whitworth et al., 2019)
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Karavolias et al. Gene Editing Agriculture Climate Change
TABLE 3 | Summary of gene-editing applications for land sparing.
Species Trait category Trait targeted Gene(s) Edited* Method Year published References
Maize Land sparing Yield Waxy CRISPR/Cas9 2020 (Gao et al., 2020)
Tomato Land sparing Yield SlCLV3, -S, -SP; CRISPR/Cas9 2017 (Huang et al., 2018)
Ground Cherry Land sparing;
Nutrition
Highly nutritive crop
modified for improved
agronomic properties
Ppr -AGO7, -SP, -SP5g CRISPR/Cas9 2018 (Lemmon et al., 2018)
Tomato Land sparing,
nutrition
Yield; Lycopene
accumulation
SP, Multiflora, Ovate,
Fasciated, Fruit Weight
2.2, Lycopene Beta
Cyclase
CRISPR/Cas9 2018 (Zsögön et al., 2018)
Rice Land sparing Yield DEP1, Gn1A CRISPR/Cas9 2018 (Huang et al., 2018)
Rice Land sparing Yield PYL 1,4,6 CRISPR/Cas9 2018 (Miao et al., 2018)
Rice Land sparing Yield OsGs3, OsGW2,
OsGn1A
CRISPR/Cas9 2019 (Zhou et al., 2019)
Wheat Land sparing Yield GW2, LPX-1,MLO CRISPR/Cas9 2018 (Wang et al., 2018)
Blunt snout sea bream Land sparing Yield mstna, mstnb CRISPR/Cas9 2020 (Sun et al., 2020)
Carp Land sparing Yield sp7, MSTN CRISPR/Cas9 2016 (Zhong et al., 2016)
Catfish Land sparing Yield MSTN CRISPR/Cas9 2017 (Khalil et al., 2017)
Cattle Land Sparing Yield MSTN ZFN, TALENs 2014, 2015 (Luo et al., 2014; Proudfoot
et al., 2015)
Chicken Land sparing Yield G0S2 CRISPR/Cas9 2019 (Park et al., 2019)
Chicken Land sparing Sex-determination Fluorescent protein into
sex chromosome
CRISPR/Cas9 2019 (Lee et al., 2019)
Goat Land sparing Yield MSTN, FGF5 CRISPR/Cas9 2015 (Wang X. et al., 2015)
Goat Land Sparing Yield MSTN TALENs, CRISPR/Cas9 2016, 2016,
2018
(Ni et al., 2014; Guo et al.,
2016; Yu et al., 2016; He
et al., 2018)
Goat Land sparing Litter size GDF9 CRISPR/Cas9 2018 (Niu et al., 2018)
Goat Land sparing,
disease
Yield Fat-1 into MSTN CRISPR/Cas9 2018 (Zhang J. et al., 2018)
Oyster Land sparing Yield MSTN CRISPR/Cas9 2019 (Yu et al., 2019)
Pig Land sparing Yield MSTN TALENs, ZFN, CRISPR/Cas9 2016, 2018,
2015, 2016,
2016, 2017
(Qian et al., 2015; Wang K.
et al., 2015; Bi et al., 2016;
Rao et al., 2016; Tanihara
et al., 2016; Wang et al.,
2017)
Pig, Buffalo Land sparing Yield MSTN CRISPR/Cas9 2018 (Su et al., 2018a)
Pig Land sparing Yield IGF2 CRISPR/Cas9 2018, 2019 (Xiang et al., 2018; Liu et al.,
2019)
Pig Land sparing Yield FBXO40 CRISPR/Cas9 2018 (Zou Y. et al., 2018)
Rabbit Land sparing Yield MSTN CRISPR/Cas9 2016 (Guo et al., 2016)
Red sea bream Land sparing Yield MSTN CRISPR/Cas9 2018 (Kishimoto et al., 2018)
Sheep Land sparing Yield MSTN CRISPR/Cas9, TALENs 2015, 2014,
2015, 2016,
2019
(Han et al., 2014; Crispo
et al., 2015; Proudfoot
et al., 2015; Li et al., 2016;
Zhang Y. et al., 2019)
Yellow catfish Land sparing Yield MSTN ZFN 2011 (Dong et al., 2011)
improvement, as was the case with rice and wheat that enabled
the Green Revolution (Khush, 1999).
Promoter Editing for Drought Tolerance in
Maize
Beyond generating knockouts, gene editing tools can also
facilitate knock-ins. Researchers have used CRISPR/Cas9 to
insert a promoter at a specific maize locus to increase drought
tolerance (Shi et al., 2017). Specifically, an alternate maize
promoter was inserted before ARGOS8, a gene associated with
drought tolerance. This precise insertion enabled greater grain
yield during flowering water stress, while maintaining yields
in normal growth conditions. This approach represents an
intragenic technique facilitated by gene-editng in which a native
maize genetic sequence was introduced at a new locus to increase
plant adaptation to an abiotic stressor.
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Karavolias et al. Gene Editing Agriculture Climate Change
TABLE 4 | Summary of gene-editing applications for nutrition.
Species Trait category Trait targeted Gene(s) Edited* Method Year
published
References
Banana Nutrition Increased beta-carotene LCYεCRISPR/Cas9 2020 (Kaur et al., 2020)
Brassica napus Nutrition Increased oleic acid content FAD2 CRISPR/Cas9 2018 (Okuzaki et al., 2018)
Camelina sativa Nutrition Reductions of linoleic acid and linolenic acid FAD2 CRISPR/Cas9 2017, 2017 (Jiang et al., 2017;
Morineau et al., 2017)
Cassava Nutrition Reduced starch PTST1, GBSS CRISPR/Cas9 2018 (Bull et al., 2018)
Maize Nutrition Reduced phytate levels IPK1 ZFN 2009 (Shukla et al., 2009)
Maize Nutrition Reduced phytic acid ZmPDS, ZmIPK1,
ZmIPK, ZmMRP4
TALENs, CRISPR/Cas9 2014 (Liang et al., 2014)
Peanut Nutrition Increased oleic acid content FAD2 TALENs 2018 (Wen et al., 2018)
Potato Nutrition Reduced starch GBSS CRISPR/Cas9 2017 (Andersson et al., 2017)
Rice Nutrition Increased amylose SBEI, SBEIIb CRISPR/Cas9 2017 (Sun et al., 2017)
Rice Nutrition Prevented cadmium uptake OsNramp5 CRISPR/Cas9 2017 (Tang L. et al., 2017)
Rice Nutrition Increased carotenoids GR-1 &GR-2
carotenoid
biosynthesis
cassettes inserted
in GSHs
CRISPR/Cas9 2020 (Dong et al., 2020)
Sorghum Nutrition Reduced kafirins K1C genes CRISPR/Cas9 2018 (Li et al., 2018)
Soybean Nutrition Altered oil levels FAD2-1A,
FAD2-1B, FAD3A
TALENs 2016 (Demorest et al., 2016)
Strawberry Nutrition Altered sugar content FvebZIPs1.1 CRISPR/Cas9 2020 (Xing et al., 2020)
Tomato Nutrition Increased anthocyanin levels ANT1, PSY1 TALENs;CRISPR/Cas9 2015 (Cermák et al., 2015; Filler
Hayut et al., 2017; Deng
et al., 2018)
Wheat Nutrition Low gluten wheat for reduced allergenicity Alpha-gliadin
array, Gli-2 locus
CRISPR/Cas9 2018 (Sánchez-León et al.,
2018)
Cattle Nutrition Reduction of milk allergen BLG ZFN 2011 (Yu et al., 2011)
Cattle Nutrition Reduction of milk allergen LacS TALENs 2018 (Su et al., 2018b)
Chicken Nutrition Less abdominal fat deposition G0S2 CRISPR/Cas9 2018 (Park et al., 2019)
Enhancing Thermotolerance of Cattle
In animals, gene editing has also been applied to mitigate abiotic
stress imposed by climate change. Acceligen, a subsidiary of
Recombinetics Inc., has undertaken an initiative to improve the
thermotolerance of cattle, with support from the Foundation for
Food and Agriculture Research (FFAR) and Semex. Researchers
are focused on replicating the SLICK phenotype originally
identified in Senepol cattle through gene editing. Variations of
this phenotype in cattle contribute to thermotolerance (Dikmen
et al., 2014; Porto-Neto et al., 2018). Conventionally bred cattle
possessing SLICK genetics are more thermotolerant, as exhibited
by lower vaginal temperatures, lower rectal temperatures, lower
respiration rates, and more sweating, thus leading to increased
milk production during summer months (Dikmen et al., 2014).
Using gene editing approaches, Acceligen seeks to replicate
SLICK genetics, to improve thermotolerance of important cattle
breeds (Bellini, 2018).
MANAGING DISEASE
A majority of diseases affecting plants and animals are anticipated
to become more widespread with climate change (Madgwick
et al., 2011; Fisher et al., 2012; Bebber, 2015; Bett et al., 2017;
Tang X. et al., 2017; Yan et al., 2017). Fortunately, many current
gene editing efforts have shown promise in conferring disease
resistance. This work will become even more necessary in coming
years as climate change increases disease severity and incidence.
Increased range of vectors, rising temperatures fostering
reproduction of pathogens, and host organisms becoming more
susceptible to pathogens are some of many climate change driven
causes of worsening disease. Gene editing can provide a solution
to managing these current and emerging global threats to
agricultural productivity precipitated by climate change (Table 2,
Figure 2).
Plant Gene Editing for Disease Resistance
In plants, genes have been identified that increase disease
resistance when knocked out. Altering genetic elements
involved in susceptibility has thus far been the primary form
of disease mitigation through gene editing. While there are
few such genes available for increasing disease resistance,
researchers have already successfully leveraged many of
these loci for heightened resistance. The following examples
demonstrate the effectiveness of knocking-out susceptibility loci
for enhanced resistance.
Frontiers in Sustainable Food Systems | www.frontiersin.org 6September 2021 | Volume 5 | Article 685801
Karavolias et al. Gene Editing Agriculture Climate Change
FIGURE 1 | Climate change will negatively impact food systems.
Increased Rice Resistance to a Range of Disease
Climate change may have varying effects on diseases across
geographies and temporal scales, as was indicated by modeling
two prevalent rice diseases in Tanzania: leaf blast and bacterial
leaf blight (Duku et al., 2016). It should be noted that these
diseases are two of the most devastating rice diseases globally. The
model indicated that bacterial leaf blight caused by Xanthomonas
oryzae pv. oryzae (PthXo2) will likely become more severe due to
climate change in Tanzania, whereas rice infection by leaf blast
caused by Magnaporthe oryzae will decrease due to changing
climate. Modeling two diseases in the same geography revealed
that climate change will not always result in increased disease
severity, thereby necessitating careful considerations of diseases
that will indeed become worse due to climate change.
Gene editing for a range of rice diseases has proven
remarkably effective. CRISPR/Cas9 was used to produce
knockouts of OsSWEET13. SWEET family genes encode
sucrose transporters that can be exploited by pathogens (Jiang
et al., 2013). Mutating this gene increased disease resistance
dramatically (Zhou et al., 2015). A similar approach to address
bacterial leaf blight used CRISPR/Cas9 to target the promoter
region of multiple OsSWEET genes in two studies (Oliva et al.,
2019; Xu et al., 2019). Lines that had been edited were broadly
resistant to many Xanthomonas pathogens. The knockout of
an alternative gene, Os8N3, similarly resulted in plants that
were also resistant to this pathogen. Os8N3 was selected as a
target based on naturally occurring resistance alleles in this gene
despite the mechanisms of resistance not being well-defined (Kim
et al., 2019). In the case of leaf blight, gene editing effectively
reduced rice susceptibility to a pathogen that is anticipated to
become more damaging in some regions of the world due to
climate change.
CRISPR/Cas9 mediated knockout of OsERF922, an ethylene
response gene previously implicated in blast resistance, had
significantly reduced lesion sizes in response to being infected
with leaf blast with no concomitant alterations to agronomic
traits (Wang et al., 2016).
Editing a eukaryotic elongation factor, eIF4G, in rice, using
CRISPR/Cas9 yielded plants entirely resistant to rice tungro
virus. Edited plants infected with virus had no detectable
viral proteins and exhibited higher yields relative to wild type
(Macovei et al., 2018). Additional efforts to engineer broad-
scale resistance to multiple rice pathogens simultaneously are
described below.
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Karavolias et al. Gene Editing Agriculture Climate Change
FIGURE 2 | Gene editing improvements for land sparing in orange, nutrition in blue, abiotic stress tolerance in red, and disease in green. (A,B) MSTN gene edits in
livestock enhance muscle yields in a variety of organisms. (B) CRISPR/Cas9 mediated MSTN edited red sea bream (left) and wild type (right) (Kishimoto et al., 2018).
Edited red sea bream exhibited 16% skeletal muscle mass increases on average. (C) TALEN enabled MSTN edited cow (right) and wild type (left) exhibit increased
overall mass and greater muscle mass (Proudfoot et al., 2015). (C) CRISPR/Cas9 promoter editing of tomato CLV3, S, SP facilitated novel variation and enhancements
to fruit size, floral architecture and overall architecture in tomato. Edited tomato (right) exhibits enlarged fruit size and increased locule number (Rodríguez-Leal et al.,
2017). (D) CRISPR/Cas9 edited LCYεenhanced beta-carotene accumulation in edited banana (right) relative to wild type (left) by nearly six fold in some lines (Kaur
et al., 2020). (E) CRISPR/Cas9 mediated editing of G0S2 in chicken (right) accumulates less abdominal and gastrointestinal fat (Park et al., 2019). (F) Improvements
to saline tolerance in rice. Knockout of OsRR22 enhances yield in high saline environments. Wild type (left) and edited rice (right) grown in 0.75% saline solution. Wild
type plants are 13% shorter than edited plants in saline conditions (Zhang A. et al., 2019). (G) CD163 locus edited by CRISPR/Cas9 yielded gene edited pigs that are
entirely resistant to porcine reproductive and respiratory virus when challenged with the virus (Whitworth et al., 2014, 2016). (H) bsr-k1 edited rice in field (right) greatly
outperforms wild type (left) after being challenged with rice blast. Edited lines performed 50% better than wild type in field after inoculation (Zhou X. et al., 2018).
Engineering Broad-Scale Resistance in Rice, Barley,
and Tomato
Some crops have been edited to establish resistance to numerous
diseases simultaneously. Engineering broad-scale resistance to
disease in staple crops could provide a single approach to
addressing many simultaneously worsening diseases (Xu et al.,
2019). An example of this approach is the editing of bsr-k1,
a rice gene identified to be important in disease resistance.
Bsr-k1 binds to defense related genes and promotes their
turnover (Zhou X. et al., 2018). Editing this gene using
CRISPR/Cas9 yielded rice plants that were simultaneously
resistant to leaf blast and bacterial leaf blight by stabilizing
important defense genes. Field trials of edited lines yielded 50%
greater when challenged with rice leaf blast in the field. Other
agronomic properties of the edited rice plants were not affected
(Zhou X. et al., 2018).
In barley, CRISPR/Cas9-mediated editing of MORC1,
a defense related gene previously identified in Arabidopsis
thaliana, simultaneously increased resistance to Blumeria
graminis f. sp. Hordei the causative agent of barley
powdery mildew and Fusarium graminearum. Edited
barley plants contained less fungal DNA and exhibited fewer
lesions (Kumar et al., 2018).
Likewise, editing of a single locus in tomato conferred
broad-spectrum resistance. Mutations to SlDMR6-1. Loss of
function mutants in Arabidopsis thaliana maintain higher levels
of salicylic acid. CRISPR/Cas9 edited tomato lines were more
resistant to P. syringae,P. capsici, and Xanthomonas spp.,
indicated by markedly less severe disease symptoms and lowered
pathogen presence (de Toledo Thomazella et al., 2016).
Managing Cassava Brown Streak Virus
In cassava, gene editing was used to address brown streak
virus which can cause yield reductions of 70% in severe
cases. Similar to host eukaryotic translation initiation factors
in rice (eiF), eIF4E isoforms encoded by the cassava genome
are required by Potyviridae viruses for infection. Simultaneous
targeting of ncbp1 and ncbp2, two such eiF4E genes, by
CRISPR/Cas9 enhanced plant resistance: root disease severity
and viral titer were lowered significantly in edited cassava lines
(Gomez et al., 2019).
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FIGURE 3 | Overview of gene editing innovation emergence over time and species. (A) Annual count of gene editing innovations since 2009. (B) Proportion of gene
editing innovations (B) in crops and livestock (C) a diverse array of crops (D) a diverse array of livestock.
Engineering Cucumber Viral Resistance
Likewise in cucumber, CRISPR/Cas9 was used to generate
deletions in the eIF4e gene to inhibit viral infections. Lines
with homozygous mutations were resistant to cucumber vein
yellowing virus, zucchini yellow mosaic virus, and papaya
ringspot virus-W as demonstrated by reduced symptoms and
viral accumulation (Chandrasekaran et al., 2016).
Wheat Powdery Mildew Mitigation
Wheat powdery mildew is also anticipated to become
increasingly severe on winter wheat in China with the
changing climate (Tang X. et al., 2017). In anticipation
of this increased disease pressure, researchers in China
have undertaken a gene editing effort to address wheat
susceptibility to this disease. Employing TALENs and
CRISPR/Cas9, researchers successfully edited the mildew
resistance locus (MLO) in the wheat genome (Wang et al.,
2014). As a result, the percentage of viable powdery mildew-
causing pathogens was effectively 0% in edited lines and
nearly 20% in wild type. Edited plants exhibited marked
improvements in powdery mildew resistance relative to
wild type.
An additional effort targeting EDR1, as an alternate
mechanism for achieving powdery mildew resistance was
undertaken using CRISPR/Cas9: edited wheat plants like
the MLO edited lines were resistant to powdery mildew
indicated by reductions in fungal structures and microcolonies
(Zhang et al., 2017).
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Karavolias et al. Gene Editing Agriculture Climate Change
Powdery Mildew Mitigation in Tomato and Grape
Gene editing for disease resistance in non-grain crops has
also been a successful endeavor. For example, in tomato, the
MLO locus was also edited using CRISPR/Cas9, leading to
the development of elite tomato varieties that are resistant
to the powdery mildew disease as indicated by heightened
hydrogen peroxide accumulation after infection with powdery
mildew (Nekrasov et al., 2017). Targeting of MLO homologs
in grapevine similarly increased powdery mildew resistance;
in grapevine there was about a 2-fold reduction in powdery
mildew sporulation in an edited line (Wan et al., 2020). It
is noteworthy that homologous loci in alternate crop species
gave rise to powdery mildew resistance when edited, providing
an example of transferable applications of gene editing among
distantly related species.
Enhancing Resistance of Tomato to Alternate
Diseases
Also in tomato, gene editing approaches have improved
resistance to bacterial speck and tomato yellow leaf curl
virus (Tashkandi et al., 2018; Ortigosa et al., 2019). Editing
of JAZ2 in tomato using CRISPR/Cas9 reduced infection by
Pseudomonas syringae pv. tomato, the causal agent of bacterial
speck, by reducing pathogen mediated stomatal opening. Edited
plants maintained significantly reduced levels of Pseudomonas
syringae pv. tomato relative to wild type. CRISPR/Cas9 mediated
resistance in tomato has also been effectively applied to manage
yellow leaf curl virus. Tomato plants were engineered to contain
guides targeting multiple sequences in the TYCV genome. Viral
accumulation was markedly decreased in engineered tomatoes
and this resistance was heritable over many generations.
Securing Banana Resistance to BSV
In bananas, banana streak virus (BSV) presents a major barrier
to breeding and distribution of banana cultivars (Musa spp.)
in various parts of the world (Tripathi J. N. et al., 2019). This
virus integrates into the B subgenome of Musa species and
remains latent until plants encounter stress such as drought.
Many important agronomic species of banana such as plantains
are affected by this virus, and breeding programs are restricted
in their ability to use Musa balbisiana as source material due to
the presence of the latent virus. Knockouts of the endogenous
virus produced lines in which 75% of edited plants remained
asymptomatic after being exposed to water stress. This is the first
study to show the efficacy of targeting an integrated plant virus in
a plant genome and provides a promising mechanism to address
a significant barrier in banana production and breeding (Tripathi
J. N. et al., 2019).
Transient Resistance in Cacao
In cacao, knockout-based improvement of resistance to
Phytopthora tropicalis was achieved in a transient assay. Cacao
plants transiently expressing CRISPR/Cas9 targeting the
TcNPR3 gene, a suppressor of disease response, exhibited smaller
lesions after infection with Phytopthora tropicalis. This work
represents the first application of gene editing in cacao, and
paves the way for future stably heritable edited lines of cacao
(Fister et al., 2018).
Grapefruit Resistance to Citrus Canker
Citrus canker is a devastating disease in most citrus fruits
especially as most commercial varieties remain susceptible
to infection. Application of CRISPR/Cas9 to grapefruit has
successfully increased resistance of edited fruit to infection.
The causative agent of citrus canker, Xanthomonas citri subsp.
citri (Xcc), is able to increase expression of CsLOB1 thus
generating cankers (Jia et al., 2016). CRISPR/Cas9 mediated
editing of CsLOB1 promoter binding sites (Jia et al., 2016) and
the CsLOB1 coding region (Jia et al., 2017) were both effective in
generating resistant grapefruit lines indicated by tremendously
reduced symptoms.
Increased Virus and Abiotic Stress Resistance in
Potato
CRISPR/Cas9 mediated editing of a gene encoding coilin
in potato plants has facilitated increased resistance to
potato virus Y. Coilin is a major structural component of
the subnuclear Cajal bodies previously implicated in virus
interactions in planta. Modification of the potato coilin gene
C-terminal domain significantly increased resistance of potato
to Potato virus Y and also increased salt and drought tolerance
(Makhotenko et al., 2019).
Curing Cotton Cancer
Cotton verticillium or “cotton cancer” is a severe disease of
cotton caused by Verticillium dahliae (Zhang Z. et al., 2018) with
little resistant germplasm available in natural populations. 14-
3-3 proteins c and d had been previously identified as negative
regulators of disease response. Knockouts of 14-3-3 c and 14-3-3
d simultaneously yielded cotton plants that were more resistant
to cotton verticillium indicated by fewer disease symptoms and
lowered pathogen presence.
Animal Gene Editing for Disease
Resistance
Diseases affecting animal hosts are projected to be affected by
climate change as well. The intersection of multiple climate and
human variables makes it difficult to determine how climate
change will affect animal pathogens (Samy and Peterson, 2016;
Bett et al., 2017). It is likely that currently temperate locations
will become more favorable to tropical vector-borne diseases,
exposing new host populations with no previous immunity and
potentially creating new disease transmission modes and patterns
(De et al., 2008). Overall, there is high confidence that diseases
and disease vectors will worsen due to climate change (Shukla
et al., in press).
Gene editing has been used to target several animal diseases;
several such studies are described below to demonstrate the
state of the field. These examples are meant to demonstrate a
substantial basis for the capacity of gene editing to ameliorate
diseases that may potentially worsen due to climate change. The
vast majority of editing for animal disease resistance centers on
the creation of disease-resistant livestock, with the exception of
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CRISPR-based gene drives in mosquitoes and other vector and
reservoir species (Esvelt et al., 2014; Hammond et al., 2016; Esvelt
and Gemmell, 2017; Champer et al., 2018; Scudellari, 2019).
Viral Resistance in Chicken
In chickens, avian leukosis viral subgroup J is a disease that
can infect meat and laying chickens, resulting in relatively
high mortality rates. Researchers used CRISPR/Cas9 and
homologous recombination to create an amino acid deletion
in the extracellular portion of the gene chNHE1 (chicken
Na+/H+exchanger type 1), which encodes the virus receptor
in chickens that allows the virus to infect cells. The deletion
was completed in chicken primordial germ cells, which through
transplantation and subsequent breeding resulted in chickens
resistant to infection by the virus (Koslov et al., 2020).
Tuberculosis and Mastitis Resistance in Cattle
Tuberculosis resistance in cattle has been addressed in two
studies. In the first study, researchers focused on the mouse
gene SP110 (SP110 Nuclear Body Protein), which controls
Mycobacterium tuberculosis (MTB) infections and induces
apoptosis in infected cells (Wu et al., 2015). The authors used
TALENickases to insert the gene into a specific location in the
bovine genome via homologous recombination; the knock-in of
this resistance gene improved tuberculosis resistance (Wu et al.,
2015). A second study using CRISPR/Cas9 was able to knock-
in the NRAMP1 gene (natural resistance-associated macrophage
protein-1, a gene associated with innate immunity) from bovine
via homologous recombination. The resulting cattle likewise
exhibited increased tuberculosis resistance (Gao et al., 2017).
Similarly, gene editing has been utilized to prevent mastitis,
the most significant disease of dairy cows. In two studies,
homologous recombination in cattle facilitated by ZFNickases
enabled the insertion of two genes that confer resistance to
infection from S. aureus, a causative agent of mastitis: the gene
encoding lysostaphin from Staphylococcus simulans (Liu et al.,
2013) and the human lysozyme (hLYZ) gene (Liu et al., 2014)
into an intron of the β-casein locus of dairy cattle. Because casein
is a protein found in dairy milk, the genes inserted into this locus
would mimic expression of β-casein and the exogenous proteins
would be present in milk produced from the edited cows (Liu
et al., 2013). Both of these studies yielded dairy cows with milk
that was able to prevent S. aureus infection of the lactating cow.
M. haemolytica is a causative agent of pneumonia in cattle.
ZFNs were used to make a precise edit in CD18, a gene encoding
a surface protein on cattle leukocytes. Leukocytes extracted from
the edited cow exhibited very low levels of cell toxicity in the
presence of M. haemolytica leukotoxin relative to wild type cattle.
Thus, a gene edit markedly improved the tolerance of gene
edited cattle to M. haemolytica, a pervasive agent of disease
(Shanthalingam et al., 2016).
Disease Resistance in Pigs
Progress has also been made in developing disease resistance
in pigs using gene editing. In a 2014 study, researchers were
able to knock out two genes, CD163 and CD1D (Whitworth
et al., 2014). The former is required for infection by porcine
reproductive and respiratory syndrome virus (PRRS virus), and
the latter is involved in innate immunity. In a follow-up to
this study, the researchers assessed the Cd163 knockout pigs for
resistance to PRRS, finding that they displayed no symptoms
when infected. In comparison, wild-type offspring developed
severe symptoms necessitating their euthanization (Whitworth
et al., 2016). Similar results were also obtained by a later study,
also using CRISPR/Cas9 editing to knock out CD163 to produce
pigs fully resistant to PRRSV (Burkard et al., 2017, 2018).
Further work in pigs was able to demonstrate the utility of
CRISPR/Cas9 to knock-in resistance to classical swine fever virus
(CSFV) at the Rosa26 locus (Xie et al., 2018). This locus is a
preferred site for transgene insertion due to its ubiquitous and
strong expression, coupled with a lack of gene-silencing effects
(Irion et al., 2007; Xie et al., 2018). The edited pigs were resistant
to CSFV, whereas all wild type pigs exhibited 100% mortality.
Researchers were also able to knock-in the C. elegans fat-1 gene
into the Rosa26 locus in pigs (Li M. et al., 2018). As fat-1 is
implicated in both disease resistance and nutritive quality of
meat, this study served as a proof-of-concept to demonstrate the
possibility of simultaneously improving the nutritional value of
pork and increasing general disease resistance in pigs. Finally, a
recent study was able to use CRISPR/Cas9 editing to knock out
the ANPEP (aminopeptidase N) gene, conferring resistance to
infections caused by coronaviruses (Whitworth et al., 2019).
Viral Resistance in Aquatic Species
Use of gene editing to combat disease in aquatic species is
more limited; the first use of a CRISPR system to test enhanced
disease resistance was in 2018 (Ma et al., 2018). Here, researchers
were able to use CRISPR/Cas9 in grass carp cell lines to knock
out gcJAM-A (grass carp Junctional Adhesion Molecule-A), a
gene involved in grass carp reovirus (GCRV) infection. When
challenged with GCRV, the edited cells were shown to suppress
viral replication (Ma et al., 2018).
In crops and livestock, genes have been identified that increase
disease resistance when knocked out. Altering genetic elements
involved in susceptibility has thus far been the primary form of
disease mitigation through gene editing for crops. Whereas, in
livestock, gene editing has facilitated the knockout and knock-
in of genes to improve disease resistance. Successful gene editing
studies in crops and animals provide a reasonable foundation for
further use of this technology to address a range of diseases, some
of which may be exacerbated by climate change.
INCREASING YIELDS
Global climate change will continue to broadly reduce crop and
livestock yields (Lobell and Gourdji, 2012). Some landscapes
will experience yield improvements, but largely climate change
stands to lower productivity (Shukla et al., in press). Coupled
with population increases, these coinciding phenomena will
necessitate the expansion of agricultural lands into currently non-
cultivated geographical areas. This expansion imposes a severe
threat to biodiversity and the associated ecological services of
non-agricultural lands. Land sparing through the augmentation
of yield can mitigate the deleterious effects of agricultural
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expansion, with gene editing as a potential tool toward this
solution (Table 3,Figure 2).
Crop Yield Improvement
Improving Rice Yields
In crop plants, a variety of gene edits have been produced
to increase yields. In rice, for example, targeting different
combinations of genes associated with yield restrictions has
produced lines with 11–68% increased yields (Huang et al., 2018;
Miao et al., 2018; Zhou et al., 2019). DEP1 and Gn1a are yield-
associated genes that have been previously characterized for their
involvement in yield attributes. One novel allele of Gn1A and
three novel alleles of DEP1 generated by CRISPR/Cas9 produced
significantly higher yields relative to wild type alleles.Gn1A
novel mutants yielded >24% which was slightly better than
the 21% yield advantage conferred by natural mutant Gn1A.
Novel mutants in DEP1 yielded up to 51% greater than WT
which is 11% greater than the naturally occurring mutants
(Huang et al., 2018).
In another case simultaneous and individual knockouts of
three yielded related genes, GS3, GW2, and Gn1a, identified to
negatively regulate grain size, width, and number, respectively,
increased yield in rice in three different cultivars. Simultaneous
KOs generated greatest yield increases, with gains of up to 68%
in one cultivar. Multiple knockouts can thus be additive in yield
improvements (Zhou et al., 2019).
CRISPR-Cas9 induced mutations in class I PYL genes
were also able to increase yield. Abscisic acid (ABA) is a.
PYL/RCARs are genes that encode receptors for ABA, a
phytohormone essential in drought responses and in seed
dormancy. Simultaneous mutations of class I PYL genes resulted
in rice plants that were higher yielding in paddy conditions.
The stomata in PYL mutants were much less responsive to
the addition of ABA, maintaining larger apertures despite the
presence of the drought signal. Thus, the mutant plants lost water
more readily. The resultant plants had larger panicles, greater
panicle branches, more tillers, and overall higher yield when
tested in field conditions. This approach could be appropriate
for rice grown in paddy conditions but would be deleterious in
conditions where water is limited. Triple knockout of PYLs 1,4,6
afforded a 30% increase in yield in well-watered conditions (Miao
et al., 2018).
Knockout-Based Wheat Yield Improvement
In wheat, simultaneous knockouts of GW2, LPX-1, and MLO
were meant to enhance yield and disease resistance. Genes
selected were previously shown in separate studies to increase
yield and wheat pathogen resistance. Homozygous, simultaneous
mutations in these three loci yielded wheat plants that had
significantly elevated grain weights and size, while disease
resistance was not evaluated (Wang et al., 2018).
Improving Yields of Waxy Maize
In maize, CRISPR/Cas9 was used to generate high amylopectin
varieties from elite cultivars by knocking out the waxy gene.
Gene edited varieties yielded 5.5 bushels more per acre relative
to high amylopectin varieties generated by conventional breeding
and were produced in less time, highlighting the throughput and
utility of gene editing relative to conventional breeding in certain
specific applications (Gao et al., 2020).
Engineering Tomato Architecture and Domestication
for Yield
Engineering of tomato architecture using CRISPR/Cas9 has
enabled improvements such as drastically increased fruit size and
altered plant morphology better suited for urban environments
(Rodríguez-Leal et al., 2017; Lemmon et al., 2018). Promoter
editing of SlCLV3, a mobile peptide important in floral stem
cell regulation, S, and inflorescence architecture gene, and
SP, an overall architecture gene, were able to generate novel
variation and enhancement in fruit size, floral architecture and
overall architecture in tomato. This study also provided major
breakthroughs in the use of gene editing cis-regulatory elements
for crop improvements.
Efforts have been made to increase yield as well as other
agronomic properties of tomatoes using CRISPR/Cas9 to
domesticate a wild tomato variety. By identifying and editing six
genes associated with key domestication traits, researchers were
able to domesticate a wild tomato relative, increasing fruit size
3-fold and fruit number 10-fold. and yield while also improving
nutrition, abiotic stress tolerance, and disease tolerance. This
study also provides the basis for future gene editing mediated
wild relative domestications (Zsögön et al., 2018).
Livestock Yield Improvement
Enhancing Livestock Yield Through MSTN Knockouts
In animal gene editing, many efforts have converged on targeting
the MSTN gene in species such as pig, cattle, sheep, goat, rabbit,
and several aquatic animals including carp, catfish, and red sea
bream (Dong et al., 2011; Han et al., 2014; Luo et al., 2014; Ni
et al., 2014; Crispo et al., 2015; Proudfoot et al., 2015; Qian et al.,
2015; Wang K. et al., 2015; Wang X. et al., 2015; Bi et al., 2016;
Guo et al., 2016; Li et al., 2016; Rao et al., 2016; Tanihara et al.,
2016; Yu et al., 2016, 2019; Zhong et al., 2016; Khalil et al., 2017;
Wang et al., 2017; He et al., 2018; Kishimoto et al., 2018; Su
et al., 2018a; Zhang J. et al., 2018; Zhang Y. et al., 2019; Sun
et al., 2020). The MSTN gene (also known as GDF8) encodes the
gene for myostatin, a growth differentiation factor that inhibits
muscle growth. In natural cattle populations MSTN mutations
underlie the double-muscled phenotype (McPherron and Lee,
1997). Successful MSTN knockout animals exhibit significantly
higher muscle mass than those with the functional MSTN gene.
Assessment of MSTN knockouts tend to vary, with some studies
comparing birth weight, body weight-to-muscle mass, muscle
fiber number, muscle weight, and muscle size between edited
and unedited animals. Combined with several bottlenecks in
efficiency of editing, comparing the outcomes of each study to
another can be challenging. ZFN, TALENs, and CRISPR/Cas9
have all been utilized to achieve MSTN-edited animals.
Studies that assessed the phenotypes of edited MSTN pigs
reported increased birth weight (Wang K. et al., 2015), body
weight-to-muscle mass ratio equaling 170% that of unedited
pigs (Rao et al., 2016), and upwards of 100% increased muscle
mass (Qian et al., 2015). Other studies reported an obvious
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double-muscled phenotype (Tanihara et al., 2016; Wang et al.,
2017), or significantly larger muscles (Bi et al., 2016), but not all
studies reported an assessment of the edited pig phenotype (Su
et al., 2018a). Comparatively fewer studies on MSTN knockouts
have been conducted in cattle, although two performed in 2014
resulted in edited animals with an obvious double-muscled
phenotype (Luo et al., 2014; Proudfoot et al., 2015).
Faster growth (Crispo et al., 2015) and increased body weight
of up to 60% (Li et al., 2016) were found in sheep, with similar
results in goats (Ni et al., 2014; Yu et al., 2016; He et al., 2018).
Studies performed as early as 2014 reported successful editing in
sheep (Proudfoot et al., 2015), but phenotypic assessment in all
cases is still lacking (Han et al., 2014), or limited to microscopy of
muscle tissue (Zhang Y. et al., 2019). One study edited both goats
and rabbits; while both exhibited increased weight ratios of biceps
and quadriceps upwards of 50%, the rabbits tended to have very
large tongues and low viability (Guo et al., 2016). Other studies
in goats successfully targeted another gene, FGF5, in addition
to MSTN (Wang X. et al., 2015), or inserted an additional gene,
fat-1, into the MSTN locus (Zhang J. et al., 2018).
MSTN has also been targeted in several aquatic species, with
the first heritable MSTN knockout in an aquaculture species
being performed by ZFN in 2011 (Dong et al., 2011). TALENs
and CRISPR/Cas9 were later used to edit carp, a tetraploid
species, although severe bone defects were present in addition to
enhanced muscle mass (Zhong et al., 2016). Successful editing
followed in several aquaculture species such as catfish, which
resulted in a 29.7% increase in catfish fry body weight (Khalil
et al., 2017), red sea bream, which resulted in a 16% increase
in muscle mass (Kishimoto et al., 2018), and blunt snout
bream, which resulted in a 7% increase in body weight (Sun
et al., 2020). Outside of fish there has also been one successful
MSTN knockout in pacific oyster, a major aquaculture bivalve
(Yu et al., 2019).
While MSTN editing appears quite promising for improving
animal yields, the drawbacks of this gene target must also be
considered. For example, increased birth weight of edited animals
can result in birthing challenges, and viability has been an issue
in several studies (Wang X. et al., 2015; Rao et al., 2016). Fine-
tuning MSTN mutations beyond complete knockouts could serve
to optimize the use of this gene as a land sparing tool. Additional
targets for increasing biomass beyond MSTN should also be
considered. For instance, of MSTN mutations, other studies in
pigs have targeted knockouts for increased muscle mass (Xiang
et al., 2018; Zou Y. et al., 2018; Liu et al., 2019).
Enhancing Livestock Yields Through Alteration of Sex
Ratios
Livestock gene editing has also been employed to alter sex
ratios of offpsring. In many production schemes, only a single
sex is required (i.e., female chickens in laying operations).
Increasing ratios of the preferred sex in offspring stands to
lower inputs and space typically allocated to rearing animals
which are unfit for the desired production. An effort in chicken
editing used CRISPR/Cas9 to insert a fluorescent protein into
the male sex chromosomes thus facilitating high-throughput sex
determination during embryogenesis (Lee et al., 2019). A system
to produce exclusively female offspring in mice by targeting
exclusively male genes has been developed with potential for
transferral to alternate mammalian species (Yosef et al., 2019).
Ongoing works seeks to improve sex-determining and sex-
biasing technologies to facilitate land and resource sparing in
livestock operations (Kurtz and Petersen, 2019; Douglas, 2020;
CSIRO, 2021), and avenues for increasing litter size in general
are being explored: one study succeeded in mutating the GDF9
gene to increase litter size in goats (Niu et al., 2018).
Land sparing is not the only method by which the ecological
consequences of agriculture can be buffered; one alternative is
land sharing (Phalan et al., 2011; Soga et al., 2014). Most of
the efforts undertaken by researchers to date are intended to be
compatible with a land sparing approach however. Gene editing
for increased yields of plants and animals has been considerably
effective in research studies and could act to prevent the sprawl
of agricultural production.
ENHANCING NUTRITION
At the end of 2019, 690 million people worldwide were suffering
from undernourishment, or the insufficient consumption of
calories (Von Grebmer et al., 2020). This pandemic stands
to worsen as climate change exacerbates yield deficits and
pest pressure. Much more pervasive however is malnutrition,
which encompasses undernourishment as well as micronutrient
deficiencies and overconsumption of calories. As of 2014, ∼2
billion individuals suffered from micronutrient deficiencies (Von
Grebmer et al., 2014).
Climate change is currently contributing to malnourishment
in several ways and is predicted to worsen. More extreme climatic
conditions will disrupt food chains and increase food prices, with
tropical and subtropical regions experiencing the worst effects of
crop yield decline (Shukla et al., in press). Prolonged droughts,
which are projected to increase, reduce root acquisition of water
soluble nutrients such as nitrate, sulfate, calcium, magnesium,
and silicon. Additionally as erratic rainfall episodes worsen, more
nitrate is expected to leach from soils (St.Clair and Lynch, 2010).
The increased level of CO2will also be detrimental to
nutritional quality of many crops (Soares et al., 2019; Shukla et al.,
in press). Wheat grown at projected mid-to-late 21st century CO2
levels has been found to have reduced protein, zinc, and iron
(Shukla et al., in press), and similar nutrient decreases have been
observed in rice, legumes, and several vegetables (Soares et al.,
2019). A modeling study predicted that climate change has placed
many fruits and vegetable crops at a high risk of going extinct
(Springmann et al., 2016). In addition, lack of reduced intake of
fruits and vegetables caused by limited access could double the
number of deaths caused by malnutrition by 2050 (Springmann
et al., 2016). Projections indicate that at the current rate of
CO2emissions, an additional 1.9% of the global population will
become deficient in zinc, 1.3% will be protein deficient, and 57%
of children and childbearing-aged women will live in geographies
at high-risk of iron deficiencies, by 2050 (Smith and Myers, 2018).
Gene editing may play a role in ameliorating the current
and future states of the malnourishment pandemic beyond
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Karavolias et al. Gene Editing Agriculture Climate Change
providing increased yields. Recent work applied to plants and
livestock has indicated that gene editing may effectively increase
desirable nutritional metabolites, reduce anti-nutrients, and alter
macronutrients in ways that can be advantageous for human
health (Table 4,Figure 2).
Increasing Beneficial Metabolites
The color pigments of crop plants such as anthocyanins,
lycopene, carotenoids are known for possessing high antioxidant
vitamins, necessary for improving nutrition and fighting disease.
Anthocyanins help in reducing inflammation and preventing
oxidative damage to cells while beta-carotene (a precursor to
vitamin A) is essential for vision and other immune functions
(Tanaka and Ohmiya, 2008). In rice, CRISPR/Cas9 editing
facilitated the insertion of carotenoid biosynthesis genes in a
precise genomic location to increase carotenoid accumulation
(Tanaka and Ohmiya, 2008) that could further advance earlier
efforts to engineer “Golden Rice.” These fortified lines stand
to benefit the poorest women and children in developing
countries with rice-dominant diets, such as Bangladesh. Likewise,
proanthocyanidins, and anthocyanins augmentation has been
pursued in rice (Zafar et al., 2020) and other species. In
tomato, CRISPR/Cas9 editing has been used to target a series
of genes, resulting in yellow, pink and purple colored tomatoes
respectively (Cermák et al., 2015; Filler Hayut et al., 2017; Deng
et al., 2018). The insertion of a strong promoter via CRISPR/Cas9
upstream of ANT1, which codes for a Myb transcription
factor, resulted in anthocyanin accumulation manifested by
an intense purple color in tomatoes (Cermák et al., 2015).
The Phytoene synthase gene (Psy1) and other carotenoid
biosynthesis genes have also been targets of genome editing that
significantly increase lycopene content in tomatoes (Li X. et al.,
2018). In addition, domestication of a wild tomato using gene
editing produced tomatoes with 500% increased accumulation
of lycopene (Zsögön et al., 2018). Dramatic enhancements of
beta-carotene in banana fruit were facilitated by a CRISPR/Cas9
mediated knockout (Kaur et al., 2020). This color variation holds
a great potential for improving consumers’ appeal for variety,
while broadening intake of healthy pigments.
Gene editing approaches have been most commonly applied
to commodity crops. However, great potential of these tools
lies in improving nutrition of non-staple, regionally relevant
fruits and vegetables. For example, the tools of gene editing
are being applied to further domesticate and improve new
“super foods” from tomato’s lesser known relatives in the
Physalis genus such as goldenberry and groundcherry (Lemmon
et al., 2018). Many of these species are rich in minerals,
macro- and micronutrients and bioactive compounds such as
antioxidants, vitamins A, B, and C, and have been long-used
as folk remedies for diseases still relevant today (Shenstone
et al., 2020). Early results suggest that CRISPR/Cas9-mediated
deletions of previously identified agronomic genes may improve
the cultivability of nutritional berries such as the ground cherry
(Lemmon et al., 2018), rendering it more economically viable for
commercial production.
The Fatty Acid Desaturase 2 (FAD2) gene determines the
levels of monounsaturated fats in most oil producing crops;
gene editing tools have been used to induce mutations in this
gene, leading to a significant change in their level. In the
emerging oil seed crop, Camelina sativa, targeted CRISPR/Cas9
editing, increased total seed oleic oil composition by more than
50% in some cases while reducing linoleic and linolenic acid
levels (Jiang et al., 2017; Morineau et al., 2017). Similarly, oleic
acid content has been improved in Brassica napus (Okuzaki
et al., 2018). Shifts in seed oil composition are thought to
be advantageous nutritionally and to extend shelf-life of oil
extracts (Jiang et al., 2017; Morineau et al., 2017). Applications of
TALEN-mediated editing to soybean facilitated the development
of a high oleic and low linolenic acid soybeans (HOLL). Oil
extracted from these modified soybeans could bypass the need for
hydrogenation, a process which generates unhealthy trans-fats
(Demorest et al., 2016). HOLL soybeans are being developed for
commercialization by Calyxt Inc. with hopes of release by 2022
(Calyxt, 2019).
Similar efforts are underway using TALEN-mediated
mutagenesis of FAD2 gene to increase oleic acid content of
peanut (Wen et al., 2018).
Modifying Macronutrients
In addition to augmenting levels of beneficial metabolites, gene
editing has made improvements to macronutrients possible. In
rice, knockouts of the SBEIIb gene associated with amylopectin
biosynthesis decreased levels of amylopectin in favor of amylose
in the grain endosperm (Sun et al., 2017). Conversely, other
food crops such as cassava have been targeted for reduced
starchy content through editing two genes involved in amylose
biosynthesis (Bull et al., 2018). A knockout of the GBSS gene
in potato using CRISPR-Cas9 also led to an altered starch
content (Andersson et al., 2017). In strawberry, gene editing
has been used to develop a continuum of altered sugar content
(Xing et al., 2020). As demonstrated, gene editing can be used
to fundamentally alter the composition of macronutrients for
nutritional improvements.
Lowering Anti-nutritional Compounds
Gene editing has also been applied to numerous plant species
to limit the accumulation of anti-nutritional components such
as phytic acid in maize, which is disruptive to the nutrition
of monogastric animals (Shukla et al., 2009; Liang et al.,
2014). To mitigate the deleterious effects of phytic acid on
iron, zinc and calcium absorption, CRISPR/Cas9 and ZFNs
were used in separate studies to mutagenize genes in the
phytic acid pathway, indicating the potential utility of gene
editing for anti-nutritional mitigation (Liang et al., 2014). In
sorghum, an important food crop in drought-prone areas, a
major class of storage proteins called kafirins leads to a poor
protein digestibility. By targeting genes that synthesize kafirins,
researchers have successfully reduced kafirin levels and improved
protein quality and digestibility (Li et al., 2018). In a similar
effort, Tang et al. engineered a rice variety to prevent the
accumulation of cadmium in rice grains using CRISPR/Cas9
(Tang L. et al., 2017).
In chickens, gene editing has driven improvements of
nutritive properties by reducing fat. Using CRISPR/Cas9 to target
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Karavolias et al. Gene Editing Agriculture Climate Change
the GOS2 gene known to influence lipid catabolism yielded
chickens with dramatically reduced abdominal fat deposition,
with no observed side-effects (Park et al., 2019). As previously
mentioned, the knockin of fat-1 in pigs enhanced the nutritional
value of pork by altering accumulation of beneficial fatty acids
(Li M. et al., 2018). Gene editing has also been used to reduce the
allergenicity of globally important commodities such as milk and
wheat (Yu et al., 2011; Su et al., 2018b;Sánchez-León et al., 2018).
In animals and crops, gene editing has been leveraged
to improve the nutritional aspects of these foodstuffs. This
technology has enabled micronutrient improvements, anti-
nutritional component reduction, macronutrient modifications,
and removal of allergens. In anticipation of the severe impacts
of climate change on nutrition, gene editing could serve as a
potent adaptive mechanism across a suite of commodities and
nutritional traits.
LIMITATIONS AND OPPORTUNITIES
Gene editing has already been applied successfully to plants
and animals in research settings to address the effects of
climate change Tables 1–4,Figures 2,3. However, there are
still significant limitations to its efficacy in enabling climate
change mitigation and adaptation. One of the most prominent
limitations of current applications is the narrow scope of
potential solutions without the use of intra-, cis-, and transgenic
approaches. In most of the examples described, researchers
produce mutations of genes whose knockout contributes
positively to a trait. However, it is more common that loss-of-
function mutation detracts from the organism’s performance.
Thus, seeking to produce improved plants solely through
loss-of-function mutation significantly limits the range of
possible improvements. Intragenics, cisgenics, and transgenics
have a proven record in research settings of improving plant
performance in a range of environments and conditions
(Klümper and Qaim, 2014; Laible et al., 2015; Steinwand
and Ronald, 2020). These approaches are able to leverage a
vast range of genomic sequences for use in plant and animal
improvements. Gene editing in conjunction with intra-, cis-,
and transgenic approaches is especially beneficial. For example,
CRISPR/Cas9 was used to precisely insert a promoter present
in the maize genome upstream of a gene that contributes to
drought tolerance (Shi et al., 2017). This novel recombination of
genetic elements native to the maize genome via CRISPR/Cas9 in
an intragenic approach improved drought tolerance. However,
genetic elements from sexually incompatible organisms can
also provide potent mechanisms for improving performance.
In cows for instance, a knock-in of a mouse resistance gene
using TALENs enhanced tuberculosis resistance (Wu et al.,
2015). Gene editing in conjunction with ICT approaches is
especially beneficial. While significant improvements through
loss-of-function gene editing and intragenic approaches
are demonstrably effective, greater opportunity exists in
leveraging the totality of genetic diversity. Thus, regulatory
barriers to use of gene editing in conjunction with ICT
approaches must be addressed to maximize the potential of
agricultural improvements.
Opportunities to address climate change with gene editing
continue to expand as new technologies emerge. For example,
alternatives to the traditional Cas9 protein for editing are
being developed. Base editors that facilitate precise nucleotide
modifications, epigenome modifiers that alter DNA confirmation
and associated expression levels, and prime editing for
precise insertion of short DNA fragments are promising
candidates in this regard (Xie et al., 2018; Roca Paixão et al.,
2019; Lin et al., 2020). Additionally, new techniques are
emerging to improve the rates of homologous recombination,
a current major limitation in plants (Huang and Puchta,
2019).
To maximize the utility of these emerging editing tools,
bottlenecks in delivery must be surmounted. For livestock, the
current largest barrier to editing tends to be the production of
homozygous, non-mosaic, gene edited animals. Two methods
currently exist to generate edited embryos prior to their transfer
to a surrogate mother: one uses somatic cell nuclear transfer
(SCNT) from an edited cell line to produce an edited embryo,
while the other uses direct editing of a zygote. In the former
case, sequencing can quickly confirm homozygous edits prior
to embryo implantation, but is burdened by the inefficiency of
SCNT. In the latter case, breeders can forgo SCNT but are unable
to verify homozygous edits until the animal is born (Bishop and
Eenennaam, 2020).
Similarly in plant regeneration, tissue culture is limiting in
its species range and efficacy. To enable a broad spectrum of
solutions in this space, tissue culture resources for a broader
set of species must be developed. Tools for increasing the
transformability of recalcitrant varieties and species are currently
underway and show great promise for gene editing-based climate
change solutions (Altpeter et al., 2016; Maher et al., 2020). These
emerging technologies could foster further improvements in
climate change performance.
Explorations of limitations beyond technical applications
are not within the scope of this review, but are germane
nonetheless. Consumer acceptance, policy frameworks, and
economic feasibility will all factor into the ultimate success of the
applications discussed.
Gene Editing Opportunities for African
Crops and Livestock
The African continent is poised to benefit greatly from advances
in gene editing research for agriculture. The Green Revolution,
which bolstered the agricultural yields in Central America,
South America, and Asia, largely overlooked African agriculture
(Toenniessen et al., 2008). Despite significant progress made
to improve food insecurity in developing nations, diseases and
pests still plague most of the region’s agriculture. Irregular
weather patterns, insect swarms and natural disasters have also
impacted agriculture in the region. Climate change will not
only affect Africa severely and variably according to the diverse
geographies, but Africa’s susceptibility to climate change hinges
on non-climate related vulnerabilities including but not limited
to high prevalence of malnutrition, low literacy rates, and high
population growth rates (Nkomo et al., 2006). As such, there
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Karavolias et al. Gene Editing Agriculture Climate Change
is much potential to focus research efforts on the crops and
livestock that are dominant and specific to Africa.
Gene Editing for Disease Resistance
African staples including African banana, plantain, cassava,
and yam are actively being edited for eventual application in
agricultural production. Comparable to crops like wheat, rice,
maize, or potatoes in other parts of the world, these staples
contribute majorly to the income of small-holder farmers in
Africa. Biotic and abiotic factors including diseases and pest
infestation, drought, flooding, etc affects the productivity of these
crops. Using gene editing, scientists are targeting these crops to
withstand these challenges.
For example, researchers are using this breeding approach
to improve resistance to cassava brown streak disease (Gomez
et al., 2019), a disease that significantly limits the production of
the crop. In addition, attempts were made to engineer resistance
to African cassava mosaic virus (ACMV). However, resistance
to ACMV was not achieved in the glasshouse experiment,
providing evidence of the mutagenic nature of this virus and
potential for further studies (Mehta et al., 2019). In banana and
plantain, a gene editing system has been applied in developing
disease resistant varieties. Using Cas9, Cas12, Cas13, and Cas14
enzymes, this system enabled the detection of gene sequences
that informed its potential application in plant disease diagnosis
(Tripathi J. N. et al., 2019).
Furthermore, a proof of concept on the potential of using
gene-editing technology for the development of novel sources
of resistance to rice yellow mottle virus; maize lethal necrosis,
a severe disease of maize in East Africa; and striga resistance in
sorghum through a Low Germination Stimulant 1 (LGS1) gene
knock-out are actively being developed by numerous researchers
in Africa (Karembu, 2021).
Gene Editing for Yield Increase and Abiotic Stress
Resistance
Targeting abiotic stresses, the first successful CRISPR/Cas9-
mediated gene knockout system in African sorghum varieties
and cowpea have recently been reported (Che et al., 2018).
Recently, gene-editing has been used to target a visual marker
gene in yam enabling potential rapid improvements by bypassing
yam’s long breeding-cycle (Syombua et al., 2019) and to develop
climate-smart banana varieties with multiple and durable
resistances to extreme temperature and drought (Tripathi L.
et al., 2019). In maize, researchers have used CRISPR/Cas9
to develop lines tolerant to drought, DNA damage, and
oxidative stress by altering the expression of poly(ADP-ribose)
polymerase (PARP), which is responsible for maintenance of
the energy homeostasis during stress conditions (Njuguna et al.,
2017).
Furthermore, researchers have provided an example of how
gene editing could be used to target and improve the yield
potential of Kabre rice, thus enhancing the domestication of
African rice landraces (Lacchini et al., 2020). Similarly, a proof of
concept is being developed for the application of genome editing
in developing wheat varieties tolerant to drought. Through
employing CRISPR-Cas9 to inactivate the Sal1 genes in wheat,
the project will determine if wheat sal1 mutant plants will show
an improved tolerance to drought stress (Karembu, 2021; USDA
ARS, 2021).
Gene Editing for Nutritional Enhancement
Nutritional enhancement is another major focus of some gene
editing research in Africa. Scientists have demonstrated how gene
editing could be used to improve the nutritional contents and
yield of cassava. Similarly, the technology is being used to reduce
the level of erucic acid in Ethiopian mustard (Brassica carinata)
varieties. While current research shows that the mustard varieties
available in market are above the acceptable level of total
fatty acid content, gene editing could be used to edit targeted
genes for improvement of nutritional content of these mustard
varieties (Karembu, 2021). In targeting both improved yield
and enhanced beta carotene content in sweet potato, scientists
are employing gene editing technology to knock out the genes
involved in converting beta carotene into other products (Joseph,
2021).
Gene Editing for Livestock Improvement
Ongoing work in the application of gene editing for African
livestock holds promise for meeting the agricultural demands
of this uniquely poised continent. Private-public partnerships
between African livestock research centers, with support and
funding from the Bill & Melinda Gates Foundation and
other donors seek to improve African livestock. Numerous
opportunities exist for editing African breeds of cows and
chickens for improved stress and disease tolerance. For example,
to combat animal trypanosomiasis, a proof of concept has been
demonstrated to introduce the Apolipoprotein L1 (ApoL 1) gene,
which has been found to confer resistance to trypanosomiasis in
primates (O’Toole et al., 2017), into goats using CRISPR/Cas9
(Karembu, 2021). Additionally, researchers are accelerating the
rate of development of the African Swine Fever Virus (ASFV)
vaccine using CRISPR/Cas9 and synthetic biology technologies
(Abkallo, 2020). Furthermore, gene editing is being used to
edit virulence genes of Theileria parva to increase the immune
response of cattle when they are vaccinated against East Coast
fever (ECF) (Karembu, 2021). To confer protection against the
Avian influenza virus (AIV) infection in poultry, researchers are
using gene-editing tools to generate variations in ANP32A, a
gene that affects AIV replication. This will enable them to predict
which of these targeted changes on the ANP32A gene will make
the most significant restrictive effect on avian influenza virus
replication (Karembu, 2021).
While most gene editing product development is at the
proof-of-concept phase, the tools present many opportunities
to potentially reduce the amount of time it takes to bring
improved crop and animal varieties to the market in sub-
Saharan Africa. Interestingly, countries like Kenya and Nigeria
have made adequate provisions in their biosafety framework
to ensure that these gene edited products will not be treated
differently from conventional crops (Komen et al., 2020). These
favorable policies will also provide the basis for future editing
with broad application in enhancing climate adaptations for
African agriculture.
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Karavolias et al. Gene Editing Agriculture Climate Change
CONCLUSION
Gene editing is an emerging and increasingly prominent
approach in plants and animals applied in response to current,
and anticipation of future, climate change. Solutions provided
by gene editing have the potential to stand alone or be adopted
concomitantly with other climate-smart solutions. The range
of gene editing applications for climate change is summarized
in Tables 1–4,Figures 2,3. Many of these applications have
converged on traits such as disease resistance, nutritional
improvements, abiotic stress tolerance and yield increases,
but these are by no means representative of the breadth of
opportunities that exist.
The emergence and application of CRISPR/Cas9 based editing
in crops and livestock has facilitated a recent increase in the
application of gene editing for climate change.
Despite its success in a research context, gene editing for
climate change has largely not yet transitioned to real application.
Adoption of these technological innovations has been stifled
by regulatory barriers, social barriers, and prohibitive policies,
among other externalities beyond the technical limitations
described. A majority of the advances in gene editing applications
for agriculture have occurred recently, which also explains, in
part, the relatively low throughput to agricultural production.
The ongoing efforts of public and private institutions alike, are
rapidly expanding on current technological innovations.
While it should be noted that gene editing is not the
sole promising agricultural improvement mechanism, the
potency of this technology in providing solutions for climate
change in agriculture cannot be overlooked. Gene editing, as
demonstrated by the numerous studies summarized herein,
stands to provide marked enhancements in agriculture to address
climate change.
DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included
in the article/supplementary material, further inquiries can be
directed to the corresponding author/s.
AUTHOR CONTRIBUTIONS
NK and WH developed the concept and completed much of
the research, and writing. SE and MA supported the writing
and editing of numerous sections. All authors contributed to the
article and approved the submitted version.
FUNDING
WH receives funding from UC Berkeley and is supported by NIH
grant DP5-OD023072. NK gratefully acknowledges financial
support from the Foundation for Food and Agriculture Research
(FFAR) Fellows program and the National Science Foundation
Graduate Research Fellowships Program. MA currently receives
support from the Genetics and Genomics Scholars Program,
North Carolina State University. SE currently receives funding
from the Bill & Melinda Gates Foundation and USDA. This work
was supported by funding for an early draft of the manuscript
which was modified for publication was provided by the Keystone
Policy Institute.
ACKNOWLEDGMENTS
We would like to acknowledge the authors whose work was
not included due to space limitations for their important
contributions to the field. We thank Maci Mueller for her careful
reading and feedback on the manuscript.
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