The Experts below are selected from a list of 29745 Experts worldwide ranked by ideXlab platform
Charles A. Gersbach - One of the best experts on this subject based on the ideXlab platform.
-
Engineering Delivery Vehicles for Genome Editing.
Annual review of chemical and biomolecular engineering, 2016Co-Authors: Christopher E Nelson, Charles A. GersbachAbstract:The field of Genome engineering has created new possibilities for gene therapy, including improved animal models of disease, engineered cell therapies, and in vivo gene repair. The most significant challenge for the clinical translation of Genome engineering is the development of safe and effective delivery vehicles. A large body of work has applied Genome engineering to genetic modification in vitro, and clinical trials have begun using cells modified by Genome Editing. Now, promising preclinical work is beginning to apply these tools in vivo. This article summarizes the development of Genome engineering platforms, including meganucleases, zinc finger nucleases, TALENs, and CRISPR/Cas9, and their flexibility for precise genetic modifications. The prospects for the development of safe and effective viral and nonviral delivery vehicles for Genome Editing are reviewed, and promising advances in particular therapeutic applications are discussed.
-
Genome Editing for Neuromuscular Diseases
Advances in Experimental Medicine and Biology, 2016Co-Authors: David G. Ousterout, Charles A. GersbachAbstract:Neuromuscular diseases are a diverse range of conditions that include myopathic and neuropathic disorders related to muscular dysfunction. Inherited neuromuscular diseases are the result of a broad spectrum of genetic mutations, including point mutations, insertions and deletions, chromosomal rearrangements, epigenetic aberrations, and repeat expansions or contractions. Targeted Genome Editing is a promising method to correct the inherited mutations underlying these disorders. Over the last decade there have been many significant advances in engineering targeted DNA-binding proteins to manipulate specific sequences of complex Genomes. These Genome Editing tools are rapidly becoming viable therapeutics that will allow the targeted addition, exchange, or removal of almost any genetic sequence in the human Genome. In this chapter, selected neuromuscular diseases representing inherited myopathies or neuropathies are discussed. The Genome Editing tools available to create targeted genetic modifications are reviewed. Promising cell- and gene-based therapies are introduced in the context of the treatment of neuromuscular disorders in combination with Genome Editing therapies. Finally, specific examples of how Genome Editing may be applied to correct the genetic basis of particular neuromuscular disorders are presented and discussed.
-
Genome Editing technologies for gene and cell therapy
Molecular Therapy, 2016Co-Authors: Morgan L Maeder, Charles A. GersbachAbstract:Gene therapy has historically been defined as the addition of new genes to human cells. However, the recent advent of Genome-Editing technologies has enabled a new paradigm in which the sequence of the human Genome can be precisely manipulated to achieve a therapeutic effect. This includes the correction of mutations that cause disease, the addition of therapeutic genes to specific sites in the Genome, and the removal of deleterious genes or Genome sequences. This review presents the mechanisms of different Genome-Editing strategies and describes each of the common nuclease-based platforms, including zinc finger nucleases, transcription activator-like effector nucleases (TALENs), meganucleases, and the CRISPR/Cas9 system. We then summarize the progress made in applying Genome Editing to various areas of gene and cell therapy, including antiviral strategies, immunotherapies, and the treatment of monogenic hereditary disorders. The current challenges and future prospects for Genome Editing as a transformative technology for gene and cell therapy are also discussed.
Sathees C. Raghavan - One of the best experts on this subject based on the ideXlab platform.
-
Modulation of DNA double-strand break repair as a strategy to improve precise Genome Editing
Oncogene, 2020Co-Authors: Ujjayinee Ray, Sathees C. RaghavanAbstract:In the present day, it is possible to incorporate targeted mutations or replace a gene using Genome Editing techniques such as customisable CRISPR/Cas9 system. Although induction of DNA double-strand breaks (DSBs) by Genome Editing tools can be repaired by both non-homologous end joining (NHEJ) and homologous recombination (HR), the skewness of the former pathway in human and other mammals normally result in imprecise repair. Scientists working at the crossroads of DNA repair and Genome Editing have devised new strategies for using a specific pathway to their advantage. Refinement in the efficiency of precise gene Editing was witnessed upon downregulation of NHEJ by knockdown or using small molecule inhibitors on one hand, and upregulation of HR proteins and addition of HR stimulators, other hand. The exploitation of cell cycle phase differences together with appropriate donor DNA length/sequence and small molecules has provided further improvement in precise Genome Editing. The present article reviews the mechanisms of improving the efficiency of precise Genome Editing in several model organisms and in clinics.
-
Modulation of DNA double-strand break repair as a strategy to improve precise Genome Editing
Oncogene, 2020Co-Authors: Sathees C. RaghavanAbstract:In the present day, it is possible to incorporate targeted mutations or replace a gene using Genome Editing techniques such as customisable CRISPR/Cas9 system. Although induction of DNA double-strand breaks (DSBs) by Genome Editing tools can be repaired by both non-homologous end joining (NHEJ) and homologous recombination (HR), the skewness of the former pathway in human and other mammals normally result in imprecise repair. Scientists working at the crossroads of DNA repair and Genome Editing have devised new strategies for using a specific pathway to their advantage. Refinement in the efficiency of precise gene Editing was witnessed upon downregulation of NHEJ by knockdown or using small molecule inhibitors on one hand, and upregulation of HR proteins and addition of HR stimulators, other hand. The exploitation of cell cycle phase differences together with appropriate donor DNA length/sequence and small molecules has provided further improvement in precise Genome Editing. The present article reviews the mechanisms of improving the efficiency of precise Genome Editing in several model organisms and in clinics.
Jennifer A Doudna - One of the best experts on this subject based on the ideXlab platform.
-
the promise and challenge of therapeutic Genome Editing
Nature, 2020Co-Authors: Jennifer A DoudnaAbstract:Genome Editing, which involves the precise manipulation of cellular DNA sequences to alter cell fates and organism traits, has the potential to both improve our understanding of human genetics and cure genetic disease. Here I discuss the scientific, technical and ethical aspects of using CRISPR (clustered regularly interspaced short palindromic repeats) technology for therapeutic applications in humans, focusing on specific examples that highlight both opportunities and challenges. Genome Editing is-or will soon be-in the clinic for several diseases, with more applications under development. The rapid pace of the field demands active efforts to ensure that this breakthrough technology is used responsibly to treat, cure and prevent genetic disease.
-
Genome Editing revolution my whirlwind year with crispr
Nature, 2015Co-Authors: Jennifer A DoudnaAbstract:Jennifer Doudna, a pioneer of the revolutionary Genome-Editing technology, reflects on how 2015 became the most intense year of her career — and what she's learnt.
Tetsuya Ishii - One of the best experts on this subject based on the ideXlab platform.
-
Somatic Genome Editing for Health: Disease Treatments and Beyond
Current Stem Cell Reports, 2016Co-Authors: Tetsuya IshiiAbstract:Genome Editing has facilitated versatile gene modifications in somatic and stem cells. Despite the early stage, therapeutic uses of ZFN and TALEN have already demonstrated promising results in the treatment of HIV and leukemia. Although the medical conditions to which Genome Editing therapy is applied are being expanded in the clinical trials, it is currently unclear whether regulatory authorities will approve Genome Editing therapy in the near future. Moreover, the widespread use of CRISPR/Cas9, in particular, is likely to lead to clinically unproven disease treatments. Furthermore, Genome Editing might be used for gene doping or cosmetic treatments. This article discusses the prospects of somatic Genome Editing for health purposes, while briefly reviewing the relevant clinical trials. Moreover, some potential ethical issues arising from the widespread use of Genome Editing are considered to discuss how Genome-Editing medicine might be appropriately integrated into the global society.
-
consumer acceptance of food crops developed by Genome Editing
Plant Cell Reports, 2016Co-Authors: Tetsuya Ishii, Motoko ArakiAbstract:One of the major problems regarding consumer acceptance of genetically modified organisms (GMOs) is the possibility that their transgenes could have adverse effects on the environment and/or human health. Genome Editing, represented by the CRISPR/Cas9 system, can efficiently achieve transgene-free gene modifications and is anticipated to generate a wide spectrum of plants. However, the public attitude against GMOs suggests that people will initially be unlikely to accept these plants. We herein explored the bottlenecks of consumer acceptance of transgene-free food crops developed by Genome Editing and made some recommendations. People should not pursue a zero-risk bias regarding such crops. Developers are encouraged to produce cultivars with a trait that would satisfy consumer needs. Moreover, they should carefully investigate off-target mutations in resultant plants and initially refrain from agricultural use of multiplex Genome Editing for better risk–benefit communication. The government must consider their regulatory status and establish appropriate regulations if necessary. The government also should foster communication between the public and developers. If people are informed of the benefits of Genome Editing-mediated plant breeding and trust in the relevant regulations, and if careful risk–benefit communication and sincere considerations for the right to know approach are guaranteed, then such transgene-free crops could gradually be integrated into society.
-
germline Genome Editing research and its socioethical implications
Trends in Molecular Medicine, 2015Co-Authors: Tetsuya IshiiAbstract:Genetically modifying eggs, sperm, and zygotes ('germline' modification) can impact on the entire body of the resulting individual and on subsequent generations. With the advent of Genome-Editing technology, human germline gene modification is no longer theoretical. Owing to increasing concerns about human germline gene modification, a voluntary moratorium on human Genome-Editing research and/or the clinical application of human germline Genome Editing has recently been called for. However, whether such research should be suspended or encouraged warrants careful consideration. The present article reviews recent research on mammalian germline Genome Editing, discusses the importance of public dialogue on the socioethical implications of human germline Genome-Editing research, and considers the relevant guidelines and legislation in different countries.
-
international regulatory landscape and integration of corrective Genome Editing into in vitro fertilization
Reproductive Biology and Endocrinology, 2014Co-Authors: Motoko Araki, Tetsuya IshiiAbstract:Genome Editing technology, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas, has enabled far more efficient genetic engineering even in non-human primates. This biotechnology is more likely to develop into medicine for preventing a genetic disease if corrective Genome Editing is integrated into assisted reproductive technology, represented by in vitro fertilization. Although rapid advances in Genome Editing are expected to make germline gene correction feasible in a clinical setting, there are many issues that still need to be addressed before this could occur. We herein examine current status of Genome Editing in mammalian embryonic stem cells and zygotes and discuss potential issues in the international regulatory landscape regarding human germline gene modification. Moreover, we address some ethical and social issues that would be raised when each country considers whether Genome Editing-mediated germline gene correction for preventive medicine should be permitted.
Andrew Camilli - One of the best experts on this subject based on the ideXlab platform.
-
Multiplex Genome Editing by natural transformation.
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Ankur B. Dalia, Emilykate Mcdonough, Andrew CamilliAbstract:Editing bacterial Genomes is an essential tool in research and synthetic biology applications. Here, we describe multiplex Genome Editing by natural transformation (MuGENT), a method for accelerated evolution based on the cotransformation of unlinked genetic markers in naturally competent microorganisms. We found that natural cotransformation allows scarless Genome Editing at unprecedented frequencies of ∼50%. Using DNA substrates with randomized nucleotides, we found no evidence for bias during natural cotransformation, indicating that this method can be used for directed evolution studies. Furthermore, we found that natural cotransformation is an effective method for multiplex Genome Editing. Because MuGENT does not require selection at edited loci in cis, output mutant pools are highly complex, and strains may have any number and combination of the multiplexed Genome edits. We demonstrate the utility of this technique in metabolic and phenotypic engineering by optimizing natural transformation in Vibrio cholerae. This was accomplished by combinatorially Editing the Genome via gene deletions and promoter replacements and by tuning translation initiation of five genes involved in the process of natural competence and transformation. MuGENT allowed for the generation of a complex mutant pool in 1 wk and resulted in the selection of a genetically edited strain with a 30-fold improvement in natural transformation. We also demonstrate the efficacy of this technique in Streptococcus pneumoniae and highlight the potential for MuGENT to be used in multiplex genetic interaction analysis. Thus, MuGENT is a broadly applicable platform for accelerated evolution and genetic interaction studies in diverse naturally competent species.