SBIR Phase I: Development of a genomic targeting drug delivery platform

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is a technology that enables the development of novel therapeutics to treat a range of serious genetic neurodegenerative diseases. The proposed drug delivery platform would help improve the understanding of the root cause of certain genetic neurodegenerative diseases. Further, new therapeutics to treat the root cause of severe neurogenerative disorders would have strong commercial potential. Currently, patients have limited treatment options and require significant and costly supportive care. New therapeutics would both improve the lives of patients and create value for insurance providers by reducing the need for costly care. This SBIR Phase I project proposes to demonstrate proof-of-concept for a genomic targeting drug-delivery platform. Unstable nucleotide repeats in the genome have been identified as the root cause of over 20 neurodegenerative conditions. These are debilitating disorders with high disease burden impacting millions of lives. Most nucleotide repeat expansion diseases are caused by a toxic gain-of-function mutation in a single allele. These diseases show dominant inheritance where most patients have a normal, unaffected copy. Silencing expression of the disease allele would address the root cause of the disease, completely halt progression of degenerative symptoms, and likely enable patients to regain lost function. The proposed effort seeks to develop a proof-of-concept allele-specific gene modulator that silences the mutant allele in myotonic dystrophy 1 (DMPK). Using this drug delivery platform, the objective is to synthesize molecules that would target transcriptional repressors specifically to the diseased DMPK allele. Using patient cells, the plan is to test for molecules that silence expression from the repeat containing diseased DMPK allele without impacting the healthy copy. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.