- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Advanced biosensing and bioanalysis techniques
- Cytokine Signaling Pathways and Interactions
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- RNA Research and Splicing
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
- interferon and immune responses
- Pluripotent Stem Cells Research
- Chromatin Remodeling and Cancer
- Monoclonal and Polyclonal Antibodies Research
- Plant Virus Research Studies
- Protein Degradation and Inhibitors
- CAR-T cell therapy research
- Cancer-related molecular mechanisms research
- Cellular Mechanics and Interactions
- RNA modifications and cancer
- Viral Infectious Diseases and Gene Expression in Insects
- BRCA gene mutations in cancer
- Gene expression and cancer classification
- DNA Repair Mechanisms
- Cardiomyopathy and Myosin Studies
- Nerve injury and regeneration
École Polytechnique
2023-2024
Nazarbayev University
2023
Centre National de la Recherche Scientifique
2023
Moscow Institute of Physics and Technology
2020
Sangamo BioSciences (United States)
2006-2019
Institut Pasteur Korea
2017
Point Richmond Tech Center
2000-2010
Lawrence Berkeley National Laboratory
2003
European Molecular Biology Laboratory
2003
Eunice Kennedy Shriver National Institute of Child Health and Human Development
1999-2000
We present a further development in the technology of sequencing by hybridization to oligonucleotide microchips (SHOM) and its application diagnostics for genetic diseases. A robot has been constructed manufacture "microchips." The microchip is an array oligonucleotides immobilized into gel elements fixed on glass plate. Hybridization with fluorescently labeled DNA was monitored real time simultaneously all two-wavelength fluorescent microscope equipped charge-coupled device camera. SHOM...
Gene knockout is the most powerful tool for determining gene function or permanently modifying phenotypic characteristics of a cell. Existing methods disruption are limited by their efficiency, time to completion, and/or potential confounding off-target effects. Here, we demonstrate rapid single-step approach targeted in mammalian cells, using engineered zinc-finger nucleases (ZFNs). ZFNs can be designed target chosen locus with high specificity. Upon transient expression these first cleaved...
Highlights•We corrected the mutant CFTR gene in cystic fibrosis iPSCs•Correction restored protein expression and function iPSC-derived epithelial cells•We observed an exquisitely sensitive, homology-dependent, allele-preferred targetingSummaryRecently developed reprogramming genome editing technologies make possible derivation of patient-specific pluripotent stem cell sources—potentially useful for development new therapeutic approaches. Starting with skin fibroblasts from patients diagnosed...
The utility of parallel hybridization environmental nucleic acids to many oligonucleotides immobilized in a matrix polyacrylamide gel pads on glass slide (oligonucleotide microchip) was evaluated. Oligonucleotides complementary small-subunit rRNA sequences selected microbial groups, encompassing key genera nitrifying bacteria, were shown selectively retain labeled target acid derived from either DNA or RNA forms the sequences. varying probe concentration normalize signals and use multicolor...
Cloning by the transplantation of somatic nuclei into unfertilized eggs requires a dramatic remodeling chromosomal architecture. Many proteins are specifically lost from nuclei, and others taken up egg cytoplasm. Recreating this exchange in vitro, we identified chromatin-remodeling nucleosomal adenosine triphosphatase (ATPase) ISWI as key molecule process. actively erases TATA binding protein association with nuclear matrix. Defining biochemistry global may facilitate efficiency cloning...
Cell lines that are mutated in interferon (IFN) responses have been critical establishing an essential role for the JAK family of nonreceptor tyrosine kinases signalling. Mutant gamma1A cells previously shown to be complemented by overexpression JAK2. Here, it is these carry a defect in, and can also by, beta-subunit IFN-gamma receptor, consistent with hypothesis mutation affects JAK2-receptor association. In contrast, mutant gamma2A lack detectable JAK2 mRNA protein. By using cells, various...
The frog Xenopus , an important research organism in cell and developmental biology, currently lacks tools for targeted mutagenesis. Here, we address this problem by genome editing with zinc-finger nucleases (ZFNs). ZFNs directed against eGFP transgene tropicalis induced mutations consistent nonhomologous end joining at the target site, resulting mosaic loss of fluorescence phenotype high frequencies. noggin gene produced tadpoles adult animals carrying up to 47% disrupted alleles, founder...
Programmed cell death-1 (PD-1) is expressed on activated T cells and represents an attractive target for gene-editing of tumor targeted prior to adoptive transfer (ACT). We used zinc finger nucleases (ZFNs) directed against the gene encoding human PD-1 (PDCD-1) gene-edit melanoma infiltrating lymphocytes (TIL). show that our clinical scale TIL production process yielded efficient modification locus, with average frequency 74.8% (n = 3, range 69.9-84.1%) alleles in a bulk population, which...
We have investigated the interactions of methyl-CpG binding transcriptional repressor MeCP2 with nucleosomal DNA. find that forms discrete complexes DNA associating methyl-CpGs exposed in major groove via methyl-CpG-binding domain (MBD). In addition to MBD, carboxyl-terminal segment facilitates both naked and nucleosome core. These observations provide a molecular mechanism by which can gain access chromatin order target corepressor further modify structure.
Zinc-finger protein transcription factors (ZFP TFs) can be designed to control the expression of any desired target gene, and thus provide potential therapeutic tools for study treatment disease. Here we report that a ZFP TF repress gene with single-gene specificity within human genome. A repressor binds an 18-bp recognition sequence promoter endogenous CHK2 gives >10-fold reduction in mRNA protein. This level repression was sufficient generate functional phenotype, as demonstrated by...
Abstract The activation of Janus protein tyrosine kinases (Jak) and STAT (signal transducer activator transcription) proteins has recently been linked to the signal transduction mechanism several cytokines. IL‐7 was observed induce a rapid dose‐dependent phosphorylation Jak 1 3 concomitantly, DNA binding activity multiple proteins. utilized by were identical those induced IL‐2 could be identified as various 5 isoforms. Moreover, induction both 3, strongly correlated with growth‐promoting...
Mammalian cells with multi-gene knockouts could be of considerable utility in research, drug discovery, and cell-based therapeutics. However, existing methods for targeted gene deletion require sequential rounds homologous recombination selection to isolate rare desired events--a process sufficiently laborious limit application individual loci. Here we present a solution this problem. Firstly, report the development zinc-finger nucleases (ZFNs) cleave three independent genes known null...