Scalable non-viral gene delivery for neuromuscular diseases - the most common adult-onset muscular dystrophy, myotonic dystrophy type 1 (DM1), is caused by the expansion of an unstable CTG-repeat…

Kinea Bio Inc. received a $306,859 Project Grant Award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846), effective September 15, 2025, with completion targeted for August 31, 2026. The award funds development of a scalable, non-viral gene delivery therapeutic platform using cell-derived nanovesicles to treat myotonic dystrophy type 1 (DM1), the most common adult-onset muscular dystrophy. This Small Business Innovation Research (SBIR) Phase 1 project will deliver in vitro validation of interfering RNA-loaded nanovesicles by screening up to 15 different small interfering RNAs (siRNAs) targeting the myotonic dystrophy protein kinase (DMPK) gene and identifying optimal constructs that reduce toxic DMPK messenger RNA in human induced pluripotent stem cells derived from DM1 patients.

The anticipated Phase 2 deliverables include preclinical efficacy data comparing nanovesicle delivery to adeno-associated virus (AAV) delivery in a DM1 mouse model, safety studies in a good laboratory practice (GLP) setting, and identification of a development candidate for regulatory advancement. The nanovesicle approach aims to provide a safer, more cost-effective alternative to viral-mediated gene therapy while establishing a therapeutic benchmark for other neuromuscular diseases with gain-of-function mutations.

Scalable non-viral gene delivery for neuromuscular diseases - the most common adult-onset muscular dystrophy, myotonic dystrophy type 1 (DM1), is caused by the expansion of an unstable CTG-repeat (50-4000 copies) in the myotonic dystrophy protein kinase (DMPK) gene. Expression of non-coding nucleotide repeats of DMPK mrna leads to toxic DMPK mrna in muscle cells triggering wide-ranging clinical features of DM, like muscle hyperexcitability (MYOTONIA), progressive skeletal muscle weakness and degeneration (MYOPATHY), cardiac conduction defects, and cataracts. There is no effective treatment for this devastating disorder. We propose to test natural cell-derived nanovesicles to modulate toxic DMPK mrna selectively and efficiently to improve safety and decrease costs compared to expensive risk-prone viral-mediated gene therapy. In phase 1 of this sbir project, we aim to validate interfering RNA-loaded nanovesicles in vitro by screening up to 15 different sirnas targeting unique regions of the DMPK gene, identify the optimal constructs that reduce toxic DMPK mrna in human induced pluripotent stem cells (IPSCS) derived from myotonic dystrophy patients, and ultimately guide the local and systemic studies in an animal model of disease proposed in phase 2. In phase 2, we propose to generate IND-enabling data for a commercial product. Once a lead nanovesicle construct is identified in phase 1, we will compare the efficacy of nanovesicle delivery in a DM1 mouse model following intramuscular (IM) injections in comparison to AAV delivery of DMPK rnai. The resulting data will inform the nomination of a development candidate (DC) for systemic dose-finding and safety studies in a GLP setting. Altogether, the experiments proposed here are aimed to advance preclinical technology for nanovesicle DMPK rnai as a viable therapy for myotonic dystrophy patients. If successful, this project can serve as a benchmark for neuromuscular diseases with similar gain-of-function mutations.