Advanced Targeting Systems — Department of Health and Human Services SBIR Phase I: 100

Description

Enhancing CRISPR based Therapeutic Interventions Via a Targeted Platform Tool Project Summary The approach described in this proposal anticipates the needs of translational drug development by designing and manufacturing a broadly applicable platform tool that eases CRISPR based therapeutic prioritization modular targeted cell specific delivery of Cas Pursuit of gene therapies for any cell based disorder becomes more efficient through the toolandapos s versatility during in vitro discovery phases continuity through in vivo preclinical pharm tox phases and potential for human clinical administration without compromising accuracy in gene altering outcomes The platform approach described in this proposal incorporates the modular flexibility of streptavidin biotin interactions to provide a tool that allows drug discovery researchers to efficiently swap out a variety of antibodies to prioritize different specific cell targets eliminating the need to create a unique CRISPR toolset for each cell type of interest By leveraging the use of antibodies to target cell based diseases as in cancer intervention the current proposal intends to harness the same specific binding properties of antibodies to deliver CRISPR Cas gene related therapies Enabling researchers to target specific cells within a larger heterogeneous cell population either in vivo or in vitro anticipates downstream drug candidate validation needs Phase I of this proposal describes an experimental design to validate the efficiency of CRISPR gene editing when incorporating cell specific targeted delivery of the Cas component Through separation at the cellular level of the targeted delivery of the gene editing instrument Cas from the delivery of nucleus targeted genetic information therapeutic potential is enhanced by this safety mechanism preventing off target gene altering in undesired cell populations Drawing on this molecular surgery technology to specifically target cell populations based on receptor expression a universal platform tool comprised of Cas attached to Streptavidin will be developed and examined for enhancement of CRISPR based therapeutic identification The development process will include Recombinant production of an enhanced specificity Cas with bespoke conjugation sites for crosslinking Conjugation and purification of a conjugate comprising streptavidin and recombinant Cas and Confirmation of selective specific delivery of Cas and retained editing ability to delete a gene within stem cell populations This project will validate the cell specific targeting approach to deliver Cas via in vitro procedures and testing with a keen eye to the needs of in vivo testing planned for Phase II Enhancing CRISPR based Therapeutic Interventions Via a Targeted Platform Tool Narrative The search for effective therapeutics often begins through examination of cell specific function in diseases and disorders drug candidates frequently target specific cells to deliver a payload that can cure or treat the problem cancer Alzheimerandapos s Disease chronic pain Parkinsonandapos s Disease to name a few The drug development platform approach described in this proposal provides a broadly applicable tool that enhances the efficiency of CRISPR based therapeutic development with targeted cell specific delivery of Cas Doing so makes any cell based disorder a candidate for gene based clinical intervention through versatility in administration without compromising accuracy in outcomes