Selection and identification of skeletal muscle-targeted RNA aptamers for therapeutic oligonucleotide delivery.. Skeletal muscle-targeted RNA aptamers

A successful gene therapy protocol for muscular dystrophies requires systemic delivery to reach all affected muscles throughout the body. Up until now, there have been no successful attempts able to overcome this difficulty and therefore, current applications are limited due to poor specificity and large diversity in efficacy. As a result, a substantial amount of the therapeutic molecules does not reach the affected muscles, but instead travels to other tissues or clears quickly from the circulation. By coupling the sequences with a target-specific vehicle the tissue specificity during delivery could be improved. The present work describes the identification of the first RNA aptamer (A01B) that specifically recognizes and enters skeletal muscle cells. This aptamer may serve as a muscle specific delivery vehicle for a wide spectrum of therapeutic sequences thus opening a new era of safe and targeted aptamer-mediated therapies for the broader group of muscular dystrophies.