11 results in Projects

A Novel Human T-Cell Platform to Define Biological Effects of Genome Editing   - Project [Biological Systems]
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Tsai Shengdar Q NIH Report
Genome editing technologies have extraordinary potential as the basis of new genomic medicines that address the underlying genetic causes of human disease; however, it is challenging to predict their long-term safety, because we do not know the consequences of potential unintended side effects of genome editing such as off-target mutations or immunogenicity. To define the biological effects of genome editing strategies, we will develop a human primary T-cell platform to sensitively detect functional effects coupled with an empirically-trained artificial intelligence models to predict them. Together, our platform will significantly improve confidence in safety assessments of promising genome editing therapeutics.
BCM-Rice Resource for the Analysis of Somatic Gene Editing in Mice   - Project [Small Animal Testing Center (SATC)]
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Heaney Jason D NIH Report
Genome editing systems have the potential to cure some of the most severe human diseases. However, there are significant efficacy and safety issues that must be addressed before this technology can be applied in clinical trials. The BCM-Rice Resource Center for the Analysis of Somatic Gene Editing in Mice will create mouse reporter models for testing genome editing technologies, and to use these animal models to test genome editing delivery technologies and new genome editors developed by other Somatic Cell Genome Editing program members.
Delivery of CRISPR Ribonucleoproteins to Airway Epithelia Using Novel Amphiphilic Peptides   - Project [Delivery Systems Initiative]
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McCray Paul B NIH Report
The proposed research is relevant to the public health because genetic and acquired diseases affecting the airways pose major disease and economic burdens. By advancing the delivery of gene editing tools, it may be possible to therapeutically modify the cells lining the airways. This novel strategy has implications for the treatment of both monogenetic and acquired lungs disease, and may have applications for other somatic cell therapies.
Efficient In Vivo RNP-Based Gene Editing in the Sensory Organ Inner Ear Using Bioreducible Lipid Nanoparticles   - Project [Delivery Systems Initiative]
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Chen Zheng-Yi NIH Report
The proposal is designed to screen lipid nanoparticles as novel materials for RNP (ribonucleoprotein) delivery of editing machinery into the mammalian sensory organ inner ear, to expand the cell types that can be edited to treat genetic hearing loss and to establish a method to perform the study in wildtype large animals. This study has direct relevance to bringing editing based therapy to clinic.
Enabling Nanoplatforms for Targeted In Vivo Delivery of CRISPR/Cas9 Riboncleoproteins in the Brain   - Project [Delivery Systems Initiative]
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Gong Shaoqin (Sarah) NIH Report
In vivo genome editing using CRISPR/Cas9 is anticipated to be the next wave of therapeutics for various major health threats, including neurodegenerative diseases. However, to date, very few Cas9-gRNA ribonucleoprotein in vivo delivery methods have been reported, and delivery to the brain has been particularly challenging. The unique nanocapsules we plan to develop will ultimately enable high efficiency neuron-targeted genome editing in the brain, thereby offering new hope to treat devastating neurodegenerative diseases.
Enhancing CRISPR Gene Editing in Somatic Tissues by Chemical Modification of Guides and Donors   - Project [Delivery Systems Initiative]
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Sontheimer Erik J NIH Report
RNA-guided CRISPR genome editing systems promise to revolutionize the treatment of inherited disease. Safe, effective, and target-tissue-specific delivery of the guide RNA that directs editing is a critical hurdle in the development of clinical applications for engineered CRISPR systems. Using strategies validated for the delivery of other categories of nucleic acid therapeutics, we have established a framework for complete chemical modification of CRISPR guides, thereby conferring in vivo stability and effective biodistribution properties. The proposed research will optimize these guides, as well as other editing components, for clinical use.
Evolving High Potency AAV Vectors for Neuromuscular Genome Editing   - Project [Delivery Systems Initiative]
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Asokan Aravind NIH Report
Recombinant adeno-associated viruses (AAV) have emerged as safe and effective vectors for clinical gene therapy applications including systemic treatment of neuromuscular diseases such as Spinal Muscular Atrophy (SMA), Duchenne Muscular Dystrophy (DMD), and Giant Axonal Neuropathy (GAN) amongst others. However, genome editing in neuromuscular tissue, in particular, is challenging. The current proposal is on a comprehensive and innovative approach to evolve high potency AAV variants for systemic neuromuscular genome editing.
Banfield Jillian , Doudna Jennifer A NIH Report
Expanding genome editing tools through exploration of new CRISPR-Cas proteins and DNA repair enzymes NARRATIVE Fundamental research on bacterial adaptive immunity uncovered the genome editing properties of CRISPR-Cas systems, and it is clear that uncultivated microbes contain more pathways and enzymes that may be useful as genome editing tools. We will combine bioinformatics and biochemistry to identify new DNA- and RNA-associating proteins and will analyze their mechanisms of action. We will focus our investigation on newly described CRISPR-Cas systems and DNA-interacting proteins that occur in conserved genomic context.
Judge Luke , Conklin Bruce , Paulk Nicole K. NIH Report
Genome editing technologies are poised to revolutionize the practice of modern medicine for the treatment of various types of genetic diseases. However, reliable testbed systems using human cells and tissues are needed to accurately predict both intended and unintended consequences of therapeutic interventions. The primary objective of this proposal is to develop and validate human tissue models capable of sensitively and accurately detecting adverse effects of genome editing on physiologic tissue function.
Novel AAVs Engineered for Efficient and Noninvasive Cross-Species Gene Editing Throughout the Central Nervous System   - Project [Delivery Systems Initiative]
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Deverman Benjamin E NIH Report
This project aims to advance the NIH Somatic Cell Genome Editing Program’s objective to identify novel delivery technologies that enable genome editing in therapeutically relevant somatic cell populations. We will use proven virus engineering methods to develop new vehicles that can deliver genome editing machinery throughout the adult mammalian central nervous system. Accomplishing this objective would pave the road for applying gene editing, and gene therapy more broadly, to the study and treatment of neurological and psychiatric disorders.
The Jackson Laboratory Gene Editing Testing Center (JAX-GETC)   - Project [Small Animal Testing Center (SATC)]
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Murray Stephen A NIH Report
The revolution in gene editing technology promises to transform the development of therapeutics to treat human disease. As part of the Somatic Cell Genome Editing consortium, the goal of this project is to build mouse resources and provide an animal model testing platform to support the optimization of novel genome editing technologies for future translational applications.

11 results in Projects

Category Type Name Description View Associated..
Project A Novel Human T-Cell Platform to Define Biological Effects of Genome Editing Genome editing technologies have extraordinary potential as the basis of new genomic medicines that address the underlying genetic causes of human disease; however, it is challenging to predict their long-term safety, because we do not know the consequences of potential unintended side effects of genome editing such as off-target mutations or immunogenicity. To define the biological effects of genome editing strategies, we will develop a human primary T-cell platform to sensitively detect functional effects coupled with an empirically-trained artificial intelligence models to predict them. Together, our platform will significantly improve confidence in safety assessments of promising genome editing therapeutics.
Project BCM-Rice Resource for the Analysis of Somatic Gene Editing in Mice Genome editing systems have the potential to cure some of the most severe human diseases. However, there are significant efficacy and safety issues that must be addressed before this technology can be applied in clinical trials. The BCM-Rice Resource Center for the Analysis of Somatic Gene Editing in Mice will create mouse reporter models for testing genome editing technologies, and to use these animal models to test genome editing delivery technologies and new genome editors developed by other Somatic Cell Genome Editing program members.
Project Delivery of CRISPR Ribonucleoproteins to Airway Epithelia Using Novel Amphiphilic Peptides The proposed research is relevant to the public health because genetic and acquired diseases affecting the airways pose major disease and economic burdens. By advancing the delivery of gene editing tools, it may be possible to therapeutically modify the cells lining the airways. This novel strategy has implications for the treatment of both monogenetic and acquired lungs disease, and may have applications for other somatic cell therapies.
Project Efficient In Vivo RNP-Based Gene Editing in the Sensory Organ Inner Ear Using Bioreducible Lipid Nanoparticles The proposal is designed to screen lipid nanoparticles as novel materials for RNP (ribonucleoprotein) delivery of editing machinery into the mammalian sensory organ inner ear, to expand the cell types that can be edited to treat genetic hearing loss and to establish a method to perform the study in wildtype large animals. This study has direct relevance to bringing editing based therapy to clinic.
Project Enabling Nanoplatforms for Targeted In Vivo Delivery of CRISPR/Cas9 Riboncleoproteins in the Brain In vivo genome editing using CRISPR/Cas9 is anticipated to be the next wave of therapeutics for various major health threats, including neurodegenerative diseases. However, to date, very few Cas9-gRNA ribonucleoprotein in vivo delivery methods have been reported, and delivery to the brain has been particularly challenging. The unique nanocapsules we plan to develop will ultimately enable high efficiency neuron-targeted genome editing in the brain, thereby offering new hope to treat devastating neurodegenerative diseases.
Project Enhancing CRISPR Gene Editing in Somatic Tissues by Chemical Modification of Guides and Donors RNA-guided CRISPR genome editing systems promise to revolutionize the treatment of inherited disease. Safe, effective, and target-tissue-specific delivery of the guide RNA that directs editing is a critical hurdle in the development of clinical applications for engineered CRISPR systems. Using strategies validated for the delivery of other categories of nucleic acid therapeutics, we have established a framework for complete chemical modification of CRISPR guides, thereby conferring in vivo stability and effective biodistribution properties. The proposed research will optimize these guides, as well as other editing components, for clinical use.
Project Evolving High Potency AAV Vectors for Neuromuscular Genome Editing Recombinant adeno-associated viruses (AAV) have emerged as safe and effective vectors for clinical gene therapy applications including systemic treatment of neuromuscular diseases such as Spinal Muscular Atrophy (SMA), Duchenne Muscular Dystrophy (DMD), and Giant Axonal Neuropathy (GAN) amongst others. However, genome editing in neuromuscular tissue, in particular, is challenging. The current proposal is on a comprehensive and innovative approach to evolve high potency AAV variants for systemic neuromuscular genome editing.
Project Expanding CRISPR-Cas Editing Technology through Exploration of Novel Cas Proteins and DNA Repair Systems Expanding genome editing tools through exploration of new CRISPR-Cas proteins and DNA repair enzymes NARRATIVE Fundamental research on bacterial adaptive immunity uncovered the genome editing properties of CRISPR-Cas systems, and it is clear that uncultivated microbes contain more pathways and enzymes that may be useful as genome editing tools. We will combine bioinformatics and biochemistry to identify new DNA- and RNA-associating proteins and will analyze their mechanisms of action. We will focus our investigation on newly described CRISPR-Cas systems and DNA-interacting proteins that occur in conserved genomic context.
Project Human Microtissues for In Situ Detection and Functional Measurement of Adverse Consequences Caused by Genome Editing Genome editing technologies are poised to revolutionize the practice of modern medicine for the treatment of various types of genetic diseases. However, reliable testbed systems using human cells and tissues are needed to accurately predict both intended and unintended consequences of therapeutic interventions. The primary objective of this proposal is to develop and validate human tissue models capable of sensitively and accurately detecting adverse effects of genome editing on physiologic tissue function.
Project Novel AAVs Engineered for Efficient and Noninvasive Cross-Species Gene Editing Throughout the Central Nervous System This project aims to advance the NIH Somatic Cell Genome Editing Program’s objective to identify novel delivery technologies that enable genome editing in therapeutically relevant somatic cell populations. We will use proven virus engineering methods to develop new vehicles that can deliver genome editing machinery throughout the adult mammalian central nervous system. Accomplishing this objective would pave the road for applying gene editing, and gene therapy more broadly, to the study and treatment of neurological and psychiatric disorders.
Project The Jackson Laboratory Gene Editing Testing Center (JAX-GETC) The revolution in gene editing technology promises to transform the development of therapeutics to treat human disease. As part of the Somatic Cell Genome Editing consortium, the goal of this project is to build mouse resources and provide an animal model testing platform to support the optimization of novel genome editing technologies for future translational applications.