Tony Le Gall

Tony Le Gall
French Institute of Health and Medical Research | Inserm · Unit of Genetics, Functional Genomics and Biotechnologies

PhD

About

83
Publications
11,616
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1,917
Citations
Citations since 2017
30 Research Items
994 Citations
2017201820192020202120222023050100150200
2017201820192020202120222023050100150200
2017201820192020202120222023050100150200
2017201820192020202120222023050100150200

Publications

Publications (83)
Article
For cystic fibrosis gene therapy, the aerosolization of genetic materials is the most relevant delivery strategy to reach the airway epithelium. However, aerosolized formulations have to resist shear forces while maintaining the integrity of plasmid DNA (pDNA) during its journey from the nebulization to the epithelial cells. Herein, we compared the...
Article
Full-text available
Antimicrobial photodynamic therapy (aPDT) depends on a variety of parameters notably related to the photosensitizers used, the pathogens to target and the environment to operate. In a previous study using a series of Ruthenium(II) polypyridyl ([Ru(II)]) complexes, we reported the importance of the chemical structure on both their photo-physical/phy...
Article
Full-text available
Women with cystic fibrosis (CF) have a significantly lower life expectancy compared to men, which is indicated by an earlier impairment of lung function due to chronic colonization with biofilm formed by Pseudomonas aeruginosa . There is growing evidence that blood serum concentrations of the steroid sex hormone estradiol (E 2 ) correlate with the...
Article
Full-text available
Aerosol lung gene therapy using non-viral delivery systems represents a credible therapeutic strategy for chronic respiratory diseases, such as cystic fibrosis (CF). Progress in CF clinical setting using the lipidic formulation GL67A has demonstrated the relevance of such a strategy while emphasizing the need for more potent gene transfer agents. I...
Article
Full-text available
We report on the fabrication and characterization of color-encoded chitosan hydrogels for the rapid, sensitive and specific detection of bacterial enzymes as well as the selective detection of a set of tested bacteria through characteristic enzyme reactions. These patterned sensor hydrogels are functionalized with three different colorimetric enzym...
Article
Full-text available
Antimicrobial photodynamic therapy (aPDT) has become a fundamental tool in modern therapeutics, notably due to the expanding versatility of photosensitizers (PSs) and the numerous possibilities to combine aPDT with other antimicrobial treatments to combat localized infections. After revisiting the basic principles of aPDT, this review first highlig...
Article
Full-text available
The mucus obstructing the airways of Cystic Fibrosis (CF) patients is a yield stress fluid. Linear and non-linear rheological analyses of CF sputa can provide relevant biophysical markers, which could be used for the management of this disease. Sputa were collected from CF patients either without any induction or following an aerosol treatment with...
Article
Introduction La mucoviscidose est une maladie génétique induite par des mutations au niveau du gène codant la protéine CFTR (Cystic Fibrosis Transmembrane conductance Regulator). La thérapie génique est une approche thérapeutique visant à introduire un transgène sain au niveau d’un tissu cible. Dans cette maladie, l’aérosol représente une voie d’ad...
Article
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RÉSUMÉ La myopathie de Duchenne est une des dystrophies musculaires les plus fréquentes, affectant 250 000 personnes à travers le monde. Elle résulte de mutations dans le gène de la dystrophine, le plus grand gène connu du génome humain. Bien que les thérapeutiques actuelles conduisent à une amélioration du pronostic clinique, l’espérance et la qua...
Article
Full-text available
An important bottleneck for non-viral gene transfer commonly relates to translocation of nucleic acids into the nuclear compartment of target cells. So-called 3NF are optimized short nucleotide sequences able to interact with the transcription factor NFκB, which can enhance the nuclear import of plasmid DNA (pDNA) carrying such motifs. In this work...
Article
Full-text available
The respiratory epithelium can be affected by many diseases that could be treated using aerosol gene therapy. Among these, cystic fibrosis (CF) is a lethal inherited disease characterized by airways complications, which determine the life expectancy and the effectiveness of aerosolized treatments. Beside evaluations performed under in vivo settings...
Article
It is reported that low concentration of amphiphilic triblock copolymers of pMeOx‐b‐pTHF‐b‐pMeOx structure (TBCPs) improves gene expression in skeletal muscle upon intramuscular co‐injection with plasmid DNA. Physicochemical studies carried out to understand the involved mechanism show that a phase transition of TBCPs under their unimer state is in...
Article
A ramified lipid alcohol, 2-hexyldecanol, was used as hydrophobic moiety to prepare at a gram scale in 3 to 4 steps, cationic amphiphiles featuring either a trimethylammonium 5, dimethylhydroxyethylammonium 6 or N-methylimidazolium 7 polar head group. Compression isotherms at the air-water interface reveal that all these cationic amphiphiles collap...
Article
Aims: This review focuses on gene transfer to skeletal muscle using hydrodynamic limb vein injection, with current applications, hurdles and possible optimizations. Discussion: Hydrodynamic limb vein injection is an in vivo locoregional gene delivery method. It consists to administrate a large volume of solution containing nucleic acid construct...
Conference Paper
Introduction/Background Animal models are required for better understanding of EOC natural history and therapy assay. We set up an experimental peritoneal carcinomatosis in an immunocompetent female rat model Fischer F 344 using a syngeneic epithelial ovarian cancer cell line NuTu 19. Methodology Twenty height female Fischer rats' F 344 were used...
Article
Full-text available
Cationic amphiphiles featuring two thioether functions in each lipid chain of bicatenar cationic amphiphiles are reported here for the first time. The physicochemical properties and transfection abilities of these new amphiphiles were compared with those of already reported analogues featuring either (i) saturated, (ii) unsaturated or (iii) mono‐th...
Article
The development of new antibacterial molecules is essential in view of the emergence of pathogenic strains resistant to multiple antibiotics. Among the infectious pathologies, pulmonary infections are particularly difficult to treat due to the complexity of lung anatomy and the presence of natural barriers such as mucus. At present, the aerosol del...
Article
Full-text available
Antibiotic resistance is a growing public health concern. Because only a few novel classes of antibiotics have been developed in the last 40 years, such as the class of oxazolidinones, new antibacterial strategies are urgently needed [1]. Nucleic acid-based antibiotics are a new type of antimicrobials. However, free nucleic acids cannot spontaneous...
Article
Twelve new quaternary ammonium sophorolipids with long alkyl chains on the nitrogen atom were synthesized starting from oleic and petroselinic acid based sophorolipids. These novel derivatives were evaluated for their antimicrobial activity against selected Gram‐negative and Gram‐positive bacteria and their transfection efficacies on three differen...
Article
The hydrophobic moiety of cationic amphiphiles plays an important role in the transfection process because its structure has an impact on both the type of the supramolecular assembly and the dynamic properties of these assemblies. These latter have to exhibit a compromise between stability and lability to efficiently compact then deliver DNA into t...
Chapter
Diseases affecting the respiratory tract are numerous and many are disabling or deadly. Nucleic acids are emerging as a new tool and a new therapeutic class of compounds that could be used to address some lung diseases. However, considering the different anatomical barriers and the physicochemical behavior of nucleic acids in the blood stream, lung...
Article
Symmetrical cyclodextrin-based 14-arm star polymers with poly(ethylene glycol) PEG branches were synthesized and characterized. Interactions of the star polymers with lipid bilayers were studied by the “black lipid membrane” technique in order to demonstrate the formation of monomolecular artificial channels. The conditions for the insertion are ma...
Article
As a growing public health concern, the worldwide spread of antimicrobial resistance urges the development of new therapies. Antibacterial photodynamic therapy (a‐PDT) may be an alternative to conventional antibiotherapy. Here, we report the synthesis and characterization of seven original reactive oxygen species (ROS) producing ruthenium(II) polyp...
Article
New synthetic pathways are proposed for the synthesis of a new set of bolaamphiphilic derivatives starting from microbiologically produced sophorolipids. A total set of 43 new derivatives was synthesized via reductive amination of a previously synthesized sophorolipid aldehyde with diamines and primary amines. The new derivatives were evaluated for...
Article
Cystic Fibrosis (CF), the most common chronic genetic disorder among the Caucasian population, is a life-threatening disease mainly due to respiratory failures resulting from chronic infections and inflammation. Although research in the pharmacological field has recently made significant progress, gene therapy still remains a promising strategy to...
Article
Full-text available
The pathophysiology of obstructive pulmonary diseases, such as cystic fibrosis, leads to the development of chronic infections in the respiratory tract. Thus, the symptomatic management of the disease requires, in particular, repetitive antibiotherapy. Besides these antibacterial treatments, certain pathologies, such as cystic fibrosis or chronic o...
Article
Neutral amphiphilic triblock ABA copolymers are of great interest to solubilize hydrophobic drugs. We reported that a triblock ABA copolymer consisting of methyl-2-oxazoline (MeOx) and tetrahydrofuran (THF) (MeOx6-THF19-MeOx6) (TBCP2) can solubilize curcumin (Cur) a very hydrophobic molecule exhibiting multiple therapeutic effects but whose insolub...
Article
Cationic lipids are widely used as synthetic vectors for gene delivery. In this short review article we report the recent developments dedicated to the synthesis of synthetic cationic phospholipids and neutral phospholipids that are specially designed for gene delivery applications. These cationic lipids that make use of a phosphorylated functional...
Article
Full-text available
Objective: Cystic Fibrosis (CF) is a genetic disorder caused by the absence or malfunction of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR). CF gene therapy would consist in delivering a normal copy of the CFTR gene in the nucleus of respiratory epithelial cells. The presence of bacteria in the pulmonary tract can alter the transpo...
Article
The ramification of cationic amphiphiles on their unsaturated lipid chains is readily achieved by using the thiol-ene click reaction triggering the formation of an inverted hexagonal phase (HII). The new ramified cationic lipids exhibit different bio-activities (transfection, toxicity) including higher transfection efficacies on 16HBE 14o-cell line...
Article
As an alternative to recombinant virus, synthetic carriers are widely developed for providing efficient and safe DNA delivery. To reach the nucleus where nucleic acids (NA) constructs are transcripted, chemical complexes have to overcome serious cellular traps such as endosomal escape and intracellular trafficking. Here, the design and the multi-st...
Article
Five quaternary ammonium amphiphilic compounds were synthesized from sophorolipid 1. These compounds were formulated in aqueous media and some of them (5 and 6) produced well-defined supramolecular aggregates which were characterized by DLS and zeta measurements. Their capacity to transfect four different eukaryotic cell lines in vitro was assessed...
Article
Six new cationic bolaamphiphiles (also called bipolar amphiphiles, bolaform amphiphiles, or bolalipids) were readily prepared by thiol-ene click reaction that engaged a mercapto-alcohol (mercapto-ethanol or mercapto-hexanol) and a cationic based lipophosphoramidate. The cationic based-lipophosphoramidates contain two lipid chains ended by an alkene...
Article
Numerous diseases affect the respiratory tract and the aerosol administration has been widely considered as an adapted and non-invasive method for local delivery. This pathway induces a lung concentration and thus also limits, systemic side effects. However, aerosol delivery of active pharmaceutical ingredients represents a real challenge, due to n...
Article
Full-text available
The objective of lung gene therapy is to reach the respiratory epithelial cells in order to deliver a functional nucleic acid sequence. To improve the synthetic carrier's efficacy, knowledge of their biodistribution and elimination pathways, as well as cellular barriers faced, depending on the administration route, is necessary. Indeed, the in vivo...
Patent
The present invention relates to novel branched amphiphilic lipids. In particular, the present invention relates to novel branched amphiphilic lipids of general formula (II). The present invention also provides a method for synthesis of said compounds of formula (II) from unsaturated amphiphilic compounds of general formula (I). The invention also...
Article
Nucleic acid delivery constitutes an emerging therapeutic strategy to cure various human pathologies. This therapy consists of introducing genetic material into the whole body or isolated cells to correct a cellular abnormality or disfunction. As with any drug, the main objective of nucleic acid delivery is to establish optimal balance between effi...
Article
Cystic Fibrosis (CF) is the most common of the hereditary genetic disorders among the Caucasian population. CF is an autosomal recessive disease that is due to mutations occurring in the gene encoding for the Cystic Fibrosis Transmembrane conductance Regulator (CFTR). Thanks to an early screening and a better care in therapies designed to address t...
Article
The structure of the cationic moiety of amphiphiles is a key factor which directly influences their transfection efficacy. Accordingly, in the present work, we have synthesized three new lipophosphoramide-based amphiphilic compounds incorporating a methoxy 5, hydroxyl 6 or dihydroxyl 7 functional group in their cationic part. Gene delivery efficaci...
Article
Full-text available
Block copolymers assembled into micelles drain a large attention to improve drug delivery. The recent drawbacks of the poly(ethylene oxide) blocks (PEO) contained in amphiphilic pluronics derivatives made of a central poly(propylene oxide) block surrounded by two PEO blocks were recently revealed, opening the way to the design of new amphiphilic bl...
Article
In this work, that aims to synthesize and evaluate new cationic lipids as vectors for gene delivery, we report the synthesis of a series of cationic lipids in which a phosphate functional group acts as a linker to assemble at a molecular scale two lipid chains and one cationic polar head. The cationic moiety, mono or di-cationic is connected to the...
Article
We report herein the synthesis of a novel family of cationic lipids, characterized by a trimethylammonium headgroup linked through a phosphate function to either two identical or two different lipid chains. The novelty of this study arises from the use of a trialkyl phosphate group to associate the hydrophobic domain to the cationic polar head. The...
Article
Gene therapy for treating inherited diseases like cystic fibrosis might be achieved using multi-modular non-viral lipid-based systems. To date, most optimizations have concerned cationic lipids rather than colipids. In this study, an original archaeal tetraether derivative was used as a colipid in combination with one or the other of two monocation...
Article
Natural giant extracellular hemoglobins (Hbs) from polychaete annelids are currently actively investigated as promising oxygen carriers. Their powerful oxygenating ability and their safety have been demonstrated in preclinical studies, motivating their development for therapeutic and industrial applications. HEMARINA-M101 (M101) is derived from the...
Article
On the basis of phosphorus chemistry, we have proposed simple and flexible access to synthetic phospholipids in which a phosphorus functional group assumes the link between two lipid chains and a cationic polar head. These cationic lipids were studied as vectors for nucleic acids delivery. Beside their capacity to carry pDNA into cells, some of the...
Article
Cationic lipids constitute a family of synthetic vectors commonly used for nucleic acids delivery. We herein report the results of a systematic study that aimed to compare the transfection efficacies of cationic lipophosphoramidates possessing either two identical lipid chains (termed symmetric cationic lipids) or two different lipid chains (non-sy...
Article
Gene therapy of diseases like cystic fibrosis (CF) would consist of delivering a gene medicine towards the lungs via the respiratory tract into the target epithelial cells. Accordingly, poly-functional nano-carriers are required in order to overcome the various successive barriers of such a complex environment, such as airway colonization with bact...
Article
Lipophosphoramidates have previously been identified as efficient vectors for gene delivery. The incorporation of functional groups that respond to a physiological stimulus is hypothesised to further improve the efficacy of this type of vector and eventually reduce its cytotoxicity. In the present work, we report the effects of the incorporation of...
Article
Full-text available
Since recombinant viral vectors have been associated with serious side effects, such as immunogenicity and oncogenicity, synthetic delivery systems represent a realistic alternative for achieving efficacy in gene therapy. A major challenge for non-viral nanocarriers is the optimization of transgene expression in the targeted cells. This goal can be...
Article
Silver based Metal Organic Framework (MOF) materials were synthesized by the reaction of phospho-benzoic acid with silver salts under hydrothermal treatment and with/without urea. According to this procedure, either both functional groups (phosphonic acid and carboxylic acid) were engaged in iono-covalent bonds with silver atoms or, on the contrary...
Article
We studied the physicochemical properties of some cationic lipophosphoramidates used as gene vectors in an attempt to better understand the link between the nature of the hydrophobic chain and both physico-chemical properties and transfection efficiency. These compounds have an arsonium head group and various chain lengths and unsaturation numbers....
Article
Full-text available
When considering a family of cationic lipids designed for gene delivery, the nature of the cationic polar head probably has a great influence on both the transfection efficacy and toxicity. Starting from a cationic lipothiophosphoramidate bearing a trimethylammonium headgroup, we report herein the impact on gene transfection activity of the replace...
Article
Lipophosphoramide-based cationic lipids are a class of synthetic vectors used for gene delivery that can be produced in multigram scale. The use of trimethylarsonium moiety as a cationic polar head was beneficial to produce efficient gene delivery vectors for in vivo applications. Moreover, this type of cationic lipid can also exhibit some bacteric...
Article
Neutral amphiphilic triblock copolymers have been shown to be efficient for gene transfection in vivo, especially by direct injection into the muscle. To contribute to a better understanding of the underlying mechanisms, in the present study, we investigated the properties of a poly(ethylene oxide-b-4-vinylpyridine) diblock copolymer as vector for...
Article
Lipophophoramidates constitute a class of synthetic vectors which were especially designed for gene delivery. In this family of compounds, the phosphorus functional group links two lipid chains to a spacer ended by a polar headgroup. Such vectors, which can readily be obtained, offer an alternative to the numerous examples of glycerolipid-based vec...
Article
The silver-based MOF material Ag3(3-phosphonobenzoate) was evaluated as a bactericidal material. A sustainable release of Ag+, which was quantified by cathodic stripping voltammetry, was responsible for bactericidal activity against the 6 bacterial strains tested.
Article
Full-text available
The synthesis of cationic lipo-thiophosphoramidates, a new family of cationic lipids designed for gene delivery, is reported herein. This new class of lipids is less polar than its oxygenated equivalent the lipo-phosphoramidates. Fluorescence anisotropy and FRET were used to determine the fluidity and fusogenicity of the lipo-phosphoramidates 3a-b...
Article
Cationic lipophosphoramidates constitute a class of cationic lipids we have previously reported to be efficient for gene transfection. Here, we synthesized and studied a novel lipophosphoramidate derivative characterized by an arsonium headgroup linked, via a phosphoramidate linker, to an unconventional lipidic moiety consisting of two diunsaturate...
Article
With the view to develop novel bioinspired nonviral vectors for gene delivery, we synthesized a series of cationic lipids with a neamine headgroup, which incorporates rings I and II of the natural antibiotic aminoglycoside neomycin B. Indeed, we reasoned that neamine might constitute a straightforward and versatile building block for synthesizing a...
Article
Cationic lipids having a phosphorus group (phosphonate or phosphoramidate) to link the lipidic part to a cationic head form an efficient family of vectors for DNA delivery. The synthesis of these types of vectors is summarized, including the recent contributions to this field.
Article
Full-text available
The selective pressures leading to the evolution and maintenance of virulence in the case of facultative pathogens are quite unclear. For example, Escherichia coli, a commensal of the gut of warm-blooded animals and humans, can cause severe extraintestinal diseases, such as septicemia and meningitis, which represent evolutionary dead ends for the p...
Article
The DNA compacting properties of polyamines (especially spermine) are well-known, hence the use of spermine as the cationic part in several synthetic DNA carriers. Here, we describe the synthesis of modified spermines, with a "lipophosphoramidate" as the lipidic part, and their use for efficient in vitro transfection. Physicochemical measurements (...
Article
Lipophosphoramidates with two different permanent cations as polar heads were synthesized and evaluated for their gene transfer activity. Physicochemical measurements (particle size, zeta potentials) and gel retardation assays were also performed. In vitro biological evaluation was conducted with A542 and HeLa cell lines, and cytotoxicity determine...