Showing 5 ideas for tag "editing"

Goal 3: Advance Translational Research

Genome Editing and Gene Therapy

There is a critical need for the establishment of strategies that will determine the efficacy, safety, and toxicity of genome editing techniques specifically in hematologic diseases.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Inherited monogenic hematologic diseases such as hemophilia, beta-thalassemia and sickle cell disease are prime targets for future application of genome editing technology. However, studies are still needed to advance our understanding of the biology of genome editing as well as determine which other disorders are amenable to genome editing correction. Emphasis on preclinical research that focuses on determining the accuracy, safety and efficiency of this technology in order to help minimize off-target mutations and reduce toxicity, is essential for effective translation of this technology into the clinic. Once preclinical efficacy is established, support will be needed for clinical vector production, toxicity testing of the vectors/reagents used, and the performance of clinical trials. The gene correction strategies developed for inherited disorders will also be attractive for other hematologic diseases, and autoimmune disorders like lupus, rheumatoid arthritis, and type I diabetes). There is also a critical need for supporting preclinical validation studies, scale-up and GMP cell manufacturing, all of which could be shared infrastructures across multiple diseases in the NHLBI portfolio.

Name of idea submitter and other team members who worked on this idea Alice Kuaban on behalf of the American Society of Hematology (ASH)

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69 net votes
87 up votes
18 down votes
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Goal 2: Reduce Human Disease

Genetic engineering in lung progenitor cells

Can genome engineering be used to correct or alter lung stem/progenitor cells to ameliorate lung disease and promote regeneration?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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-15 net votes
3 up votes
18 down votes
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Goal 3: Advance Translational Research

Use isogenic iPS cells to advance Precision Medicine

The goals of Precision Medicine can be achieved if we determine the biological basis of disease-associated variants for NHLBI diseases. Advances in genetic research have yielded hundreds of disease-associated DNA polymorphisms, yet we lack robust methods to experimentally test their functional relevance in human cells. Determining the molecular and cellular basis of human phenotypic variation is one of the great challenges... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Identifying how disease mutations result in cellular phenotypes will provide an experimental basis for Precision Medicine. Advances in genome engineering and iPS cell technology now offer a unique opportunity for NHLBI researchers to make a focused effort to produce isogenic disease models, to determining the function of putative disease loci. Just a few years ago, the barriers to this type of project seemed insurmountable, as iPS cells were made with damaging DNA insertions, designer nucleases were difficult to make, complex material-transfer agreements (MTAs) inhibited the open sharing of reagents, and cell-engineering methods were cumbersome. Remarkably, all of these barriers have fallen substantially in recent years, to reveal strategic new opportunities. The phenotypes are determined in isogenic human iPS-models, these observations can be applied to animal models, and human clinical studies.

Feasibility and challenges of addressing this CQ or CC

Progress towards this goal is being made, but slow pace does not meet opportunity that the NHLBI community has. The NHLBI has a much larger opportunity than other institutes because so many genetic variants have already been determined via excellent genetic studies using robust physiological phenotypes. The genetic variants provide hypotheses that are ripe for direct experimental testing in isogenic iPS cell models. Fortunately, many diseases of interest to NHLBI can be modeled in iPS-derived tissues. Other part of NIH (e.g. NIMH, NIDA, NIAAA ) lack abundance of high probability genetic "hits" that NHLBI now has. NHLBI should take advantage of this opportunity.

Name of idea submitter and other team members who worked on this idea Bruce Conklin

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-19 net votes
8 up votes
27 down votes
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Goal 3: Advance Translational Research

Novel Technologies & Clinical Therapeutics

How can NHLBI harness the power of novel technologies involving nucleic acid delivery and gene editing for clinical therapeutics?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea Cystic Fibrosis Foundation

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-2 net votes
2 up votes
4 down votes
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