Project 462420

To date, approximately 7,000 rare genetic diseases have been identified, which affect 1 in 12 or nearly 3 million Canadians combined. Artificial small DNA-like molecules called antisense oligonucleotides (AOs) are emerging tools for the treatment of genetic diseases. In the last 8 years, approximately10 AOs have been approved by the FDA and other regulatory bodies worldwide for the treatment of various genetic diseases, including Duchenne muscular dystrophy (DMD) among others. Dr. Yokota's previous study demonstrated for the first time that AOs can restore gene function by modulating gene transcripts and improved muscle strength in a severe animal model of DMD. This study directly led to a collaboration with a pharmaceutical company and the development of viltolarsen, an AO drug for the treatment of DMD, which was approved by the FDA in 2020. Viltolarsen is the first and only FDA-approved drug that clearly restored dystrophin, a muscle-supporting protein, and improved muscle function in clinical trials. Although promising, AO-mediated therapy faces a major challenge, limited in vivo delivery. No effective delivery tool has been developed for AOs, leading to limited efficacy. Therefore, effective yet safe delivery of AOs is urgently needed. Our proposed research aims to develop a new platform for the delivery of AO-mediated therapy. Recently, Dr. Yokota's research team identified a novel T-cell-derived cell-penetrating peptide that can efficiently deliver AOs to bodywide tissues, including the heart, brain, and skeletal muscle among others, as published in a recent article in PNAS. Our team launched a startup company OligomicsTx to facilitate the commercialization of this technology. Overall, we will develop novel delivery tools for AO-mediated therapy that can be used to treat most genetic diseases. Developing a new AO delivery method will lead to effective AO therapies and positively impact the lives of people with many genetic diseases.