Ting Yang's research while affiliated with University of California, San Diego and other places

Publications (32)

Preprint
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Escalating vector disease burdens pose significant global health risks, so innovative tools for targeting mosquitoes are critical. We engineered an antiviral strategy termed REAPER (vRNA Expression Activates Poisonous Effector Ribonuclease) that leverages the programmable RNA-targeting capabilities of CRISPR Cas13 and its potent collateral activity...
Article
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As a major insect vector of multiple arboviruses, Aedes aegypti poses a significant global health and economic burden. A number of genetic engineering tools have been exploited to understand its biology with the goal of reducing its impact. For example, current tools have focused on knocking-down RNA transcripts, inducing loss-of-function mutations...
Preprint
Full-text available
As a major insect vector of multiple arboviruses, Aedes aegypti poses a significant global health and economic burden. A number of genetic engineering tools have been exploited to understand its biology with the goal of reducing its impact. For example, current tools have focused on knocking-down RNA transcripts, inducing loss-of-function mutations...
Article
Full-text available
CRISPR-based genetic engineering tools aimed to bias sex ratios, or drive effector genes into animal populations, often integrate the transgenes into autosomal chromosomes. However, in species with heterogametic sex chromsomes (e.g. XY, ZW), sex linkage of endonucleases could be beneficial to drive the expression in a sex-specific manner to produce...
Article
The development of an extensive toolkit for potential point-of-care diagnostics that is expeditiously adaptable to new emerging pathogens is of critical public health importance. Recently, a number of novel CRISPR-based diagnostics have been developed to detect SARS-CoV-2. Herein, we outline the development of an alternative CRISPR nucleic acid dia...
Article
Originally from Asia, Drosophila suzukii Matsumura is a global pest of economically important soft-skinned fruits. Also commonly known as spotted wing drosophila, it is largely controlled through repeated applications of broad-spectrum insecticides by which resistance has been observed in the field. There is a pressing need for a better understandi...
Article
Full-text available
The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and Zika virus, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular ge...
Article
Full-text available
Engineered reproductive species barriers are useful for impeding gene flow and driving desirable genes into wild populations in a reversible threshold-dependent manner. However, methods to generate synthetic barriers have not been developed in advanced eukaryotes. To overcome this challenge, we engineered SPECIES (Synthetic Postzygotic barriers Exp...
Preprint
Full-text available
The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and zika, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular genetic...
Preprint
Full-text available
Originally from Asia, Drosophila suzukii (Matsumura, 1931, Diptera: Drosophilidae) is presently a global pest of economically important soft-skinned fruits. Also commonly known as spotted wing Drosophila (SWD), it is largely controlled through repeated applications of broad-spectrum insecticides. There is a pressing need for a better understanding...
Preprint
The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and zika, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular genetic...
Preprint
Full-text available
The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and zika, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular genetic...
Article
CasRx, a member of the RNA-targeting Cas13 family, is a promising new addition of the CRISPR/Cas technologies in efficient gene transcript reduction with an attractive off-target profile at both cellular and organismal levels. It is recently reported that the CRISPR/CasRx system can be used to achieve ubiquitous and tissue-specific gene transcript...
Article
Since its first emergence from China in late 2019, the SARS-CoV-2 virus has spread globally despite unprecedented containment efforts, resulting in a catastrophic worldwide pandemic. Successful identification and isolation of infected individuals can drastically curtail virus spread and limit outbreaks. However, during the early stages of global tr...
Preprint
Full-text available
Since its first emergence from China in late 2019, the SARS-CoV-2 virus has spread globally despite unprecedented containment efforts, resulting in a catastrophic worldwide pandemic. Successful identification and isolation of infected individuals can drastically curtail virus spread and limit outbreaks. However, during the early stages of global tr...
Preprint
Full-text available
Engineered reproductive species barriers are useful for impeding gene flow and driving desirable genes into wild populations in a reversible threshold-dependent manner. However, methods to generate synthetic barriers are lacking in advanced eukaryotes. To overcome this challenge, we engineered SPECIES ( S ynthetic P ostzygotic barriers E xploiting...
Article
CRISPR-Cas genome editing technologies have revolutionized the fields of functional genetics and genome engineering, but with the recent discovery and optimization of RNA-targeting Cas ribonucleases, we may soon see a similar revolution in the study of RNA function and transcriptome engineering. However, to date, successful proof of principle for C...
Preprint
Full-text available
CRISPR-Cas genome editing technologies have revolutionized the fields of functional genetics and genome engineering, but with the recent discovery and optimization of RNA-targeting Cas ribonucleases, we may soon see a similar revolution in the study of RNA function and transcriptome engineering. However, to date, successful proof-of-principle for C...
Article
Full-text available
Numerous plants and animals harbor selfish B chromosomes that “drive” or transmit themselves at super-Mendelian frequencies, despite long-term fitness costs to the organism. Currently, it is unknown how B chromosome drive is mediated, and whether B-gene expression plays a role. We used modern sequencing technologies to analyze the fine-scale sequen...
Article
Full-text available
Aedes aegypti, the principal mosquito vector for many arboviruses that increasingly infect millions of people every year. With an escalating burden of infections and the relative failure of traditional control methods, the development of innovative control measures has become of paramount importance. The use of gene drives has sparked significant e...
Preprint
Full-text available
Numerous plants and animals harbor selfish B chromosomes that “drive,” or transmit themselves at higher-than-Mendelian frequencies, despite long-term fitness costs to the organism. Currently it is unknown how B chromosome drive is mediated, and whether B-gene expression plays a role. We used modern sequencing technologies to analyze the fine-scale...
Article
Full-text available
Background: The mosquito Aedes aegypti has a wide variety of sensory pathways that have supported its success as a species as well as a highly competent vector of numerous debilitating infectious pathogens. Investigations into mosquito sensory systems and their effects on behavior are valuable resources for the advancement of mosquito control stra...
Preprint
Full-text available
Aedes aegypti , the principal mosquito vector for many arboviruses that causes yellow fever, dengue, Zika, and chikungunya, increasingly infects millions of people every year. With an escalating burden of infections and the relative failure of traditional control methods, the development of innovative control measures has become of paramount import...
Preprint
Full-text available
Aedes aegypti have a wide variety of sensory pathways that have supported success as a species as well as a highly competent vector of numerous debilitating infectious pathogens. Investigations into mosquito sensory systems and their effects on behavior are valuable resources for the advancement of mosquito control strategies. Numerous studies have...
Article
Full-text available
Significance Here we describe a fully functional gene drive system constructed in a major worldwide crop pest, Drosophila suzukii . This system is composed of a synthetic Medea drive with a maternal miRNA “toxin” and a zygotic “antidote,” and we demonstrate that it can bias inheritance with 100% efficiency and can persist in a population given high...
Article
Full-text available
Significance Aedes aegypti is the principal vector of multiple arboviruses that significantly affect human health, including dengue, chikungunya, and zika. Development of tools for efficient genome engineering in this mosquito will not only lay the foundation for the application of genetic control strategies, but will also accelerate basic research...
Preprint
Full-text available
Synthetic gene drive systems possess enormous potential to replace, alter, or suppress wild populations of significant disease vectors and crop pests; however, their utility in diverse populations remains to be demonstrated. Here, we report the creation of the first-ever synthetic Medea gene drive element in a major worldwide crop pest, D. suzukii...
Preprint
Full-text available
The development of CRISPR/Cas9 technologies has dramatically increased the accessibility and efficiency of genome editing in many organisms. In general, in vivo germline expression of Cas9 results in substantially higher activity than embryonic injection. However, no transgenic lines expressing Cas9 have been developed for the major mosquito diseas...

Citations

... As mentioned in the following section, other binary expression systems, such as LexA/LexAop [48] and CRISPR/dCas9-VPR-based transactivators, have been used in fruit flies [48][49][50] and recently in mosquitoes [51], alone or in combination with the Gal4/UAS and the Q systems. Combining the binary system in mosquitoes will allow the development of sensors of neuronal response and strengthen our understanding of the transmission of sensory input to higher brain centers. ...
... Temporal and spatial control of gene expression can aid in understanding details of gene and/or pathway function by regulating timing and/or dosage of gene transcription and products. Temporal control of sterile insect technologies like precision-guided sterile insect technique (pgSIT) can be a powerful and financially impactful tool for scaling up large populations of pest species for release and population control (Kandul et al. 2019(Kandul et al. , 2021(Kandul et al. , 2022. Heat-shock inducible Cas9 has been used in multiple organisms to induce programmed mutations, including in rice (Nandy et al. 2019) and Drosophila (Kandul et al. 2021), however these systems still reveal Cas9 activity without heat shock. ...
... The design analysed here does not rely on expression of the sex chromosomes during meiosis, though it does require expression from the Y-chromosome in the germline. Such expression has been observed for a marker gene in An. gambiae [36] and for Cas9 in Drosophila melanogaster [37]. ...
... We genetically encoded CasRx expression in mosquitoes and demonstrated its efficacy by targeting two non-essential genes. Subsequently, we biochemically screen the activity of gRNAs targeting CHIKV using a sensitive enzymatic nucleic acid sequence reporter (SENSR) 19 . We then use these effective gRNAs to engineer an antiviral sensor in Aedes aegypti termed vRNA Expression Activates Poisonous Effector Ribonuclease (REAPER). ...
... In D. suzukii, we previously generated four dsRed-tagged strains in which the Cas9 endonuclease is expressed under different promoters: vasa-Cas9 (vasCas9), BicC-Cas9 (BicC.Cas9), nanos-Cas9 (nosCas9), and Ubiq-Cas9 (UbiCas9). 46 Prior data determined that nosCas9 induced the least F 1 phenotypic disruption in combination with gRNAs targeting the white or yellow loci and that UbiCas9 incurred some fitness costs to its carriers. ...
... In tandem with improved and expanding assemblies of the Ae. aegypti genome and various transcriptomes [8][9][10], pivotal tools in the development of genetic-based vector control strategies have been the reduction of transcript levels using RNAi [11], germline transformation using transposable elements [12], and programmable DNA targeting-using Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) [13][14][15]. For example, RNAi and other small RNAs have been instrumental in generating knock-down phenotypes within the mosquito [16][17][18] as well as a method for reducing viral transcript numbers [18][19][20][21][22]. ...
... We recently developed an alternative platform for the generation and sex separation of sterile males using the CRISPR-mediated precision guided SIT (pgSIT) technology 15,16 . This technology mechanistically relies on lethal/sterile mosaicism, mediated by the precision and accuracy of CRISPR, to simultaneously disrupt specific genes essential for female viability and male fertility during development, ensuring the exclusive production of sterile males. ...
... Prior to any gene drive field release, these commitments include fair partnership and transparency, testing of product efficacy and safety, regulatory evaluation and risk/benefit analysis, and developing monitoring and mitigation strategies. Additionally, given the concerns related to non-confinable gene drive technologies observed in this study, the Akbari lab is prioritizing research on confineable technologies for controlling populations such as self-limiting drives (Li et al., 2020) and GE-SIT systems (Li et al., 2021). This is an example of how this work on community and stakeholder engagement has directly informed research and development within Team California. ...
... The Cas13 protein family represents a programmable RNA-targeting clustered regularly interspaced short palindromic repeats (CRISPR) system, which can mediate RNA knockdown with high efficiency and specificity relative to other existing RNA interference approaches Cox et al., 2017;Gootenberg et al., 2017;Smargon et al., 2017;Yan et al., 2018). Among Cas13 family, RfxCas13d (CasRx) has the smallest size and highest RNase activity (Chuang et al., 2021;Jiang et al., 2020;Konermann et al., 2018;Kushawah et al., 2020;Li et al., 2021;Sun et al., 2021;Yan et al., 2018;Zhang et al., 2020;Zhou et al., 2020b). ...
... Cas13d ribonuclease is derived from Ruminococcus flavefaciens (CasRx). To expand CRISPR-based diagnostic strategies, researchers have used Cas13d for the first time in molecular diagnostics by developing a system for detecting SARS-CoV-2 called SENSR (Sensitive Enzymatic Nucleic-acid Sequence Reporter) as a modification of SHERLOCK (Brogan et al., 2020). The first step of SENSR is isothermal amplification, an initial 45-minute isothermal pre-amplification reaction by RT-RPA that generates a short dsDNA amplicon containing the T7 promoter sequence that is processed into the final RNA target sequence. ...