Therapeutic gene editing: delivery and regulatory perspectives

Authors: Gayong SHIM, Dongyoon KIM, Gyu Thae PARK, Hyerim JIN, Soo-Kyung SUH, Yu-Kyoung OH
DOI: 10.1038/aps.2017.2


Gene-editing technology is an emerging therapeutic modality for manipulating the eukaryotic genome by using target-sequencespecific engineered nucleases. Because of the exceptional advantages that gene-editing technology offers in facilitating the accurate correction of sequences in a genome, gene editing-based therapy is being aggressively developed as a next-generation therapeutic approach to treat a wide range of diseases. However, strategies for precise engineering and delivery of gene-editing nucleases, including zinc finger nucleases, transcription activator-like effector nuclease, and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated nuclease Cas9), present major obstacles to the development of gene-editing therapies, as with other gene-targeting therapeutics. Currently, viral and non-viral vectors are being studied for the delivery of these nucleases into cells in the form of DNA, mRNA, or proteins. Clinical trials are already ongoing, and in vivo studies are actively investigating the applicability of CRISPR/Cas9 techniques. However, the concept of correcting the genome poses major concerns from a regulatory perspective, especially in terms of safety. This review addresses current research trends and delivery strategies for gene editing-based therapeutics in non-clinical and clinical settings and considers the associated regulatory issues.
Keywords: gene editing; zinc finger nuclease; transcription activator-like effector nuclease; CRISPR/Cas9; delivery system; regulation; safety