Call for Papers: Expanding the Scale and Scope of Therapeutic Gene Editing
Authors: Hans-Peter Kiem, Nicole N. Gaudelli, Fyodor D. Urnov, Robert M. Frederickson, Roland W. Herzog
Journal: Molecular Therapy (2020)

The approval over the past decade of viral gene therapy and RNAi/antisense-based medicines for both genetic diseases and cancer has provided a comprehensive preclinical, regulatory, and commercial framework to advance a nucleic acid-directed experimental therapy through first-in-human trials and licensure. These events have paved the way for development of genome/gene editing approaches for a broad range of disease indications, and the editors are happy to announce a special issue of Molecular Therapy that aims to focus on this important area. Nicole Gaudelli (Beam Therapeutics), Fyodor Urnov (Unuversity of California Berkeley), and Hans-Peter Kiem (Fred Hutchinson Cancer Research Center) have graciously agreed to serve as co-guest editors of this special issue, which we hope to publish in May of 2021 so as to coincide with the annual meeting of the American Society of Gene and Cell Therapy. Following the 2012 discovery that programmable RNA-directed nucleases, such as Cas9 derived from CRISPR-based bacterial adaptive immune systems, can be used for genome editing in mammalian cells, along with the continued development of this and other editing platforms, progress toward moving these gene editing technologies to the clinic has accelerated. Excitingly, the first-in-human trials utilizing gene editing approaches are currently underway for both ex vivo (HIV, cancer, the hemoglobinopathies) and in vivo (hemophilia, lysosomal storage diseases, and blindness) applications. Key data from these efforts have not revealed, to date, known treatment-related severe adverse events, and in the case of the hemoglobinopathies, preliminary data suggest the feasibility of attaining a major amelioration or even elimination of disease symptoms following a one-time administration of an autologous gene-edited cell product. By extension, the full realization of the hope and promise of these transformative therapies is on the horizon and the coming decade will likely feature the approval of a number of gene editing-based medicines. While the challenge of engineering nuclease-based gene editing tools that evoke a desired genetic change at a given locus efficiently and with robust specificity has largely been solved, the focus of the current effort, and, accordingly, of this upcoming special issue of Molecular Therapy, is to illuminate (1) approaches that do not require a double-stranded DNA break (DSB) to drive a desired genetic outcome; (2) the engineering of more versatile, facile, and safe methods to deliver the genome editing machinery ex vivo and in vivo; (3) the development of ways to profile the on- and off-target activities of genome editing enzymes commensurate with the need to apply it to chronic, rather than acute, disease; (4) the establishment of robust preclinical paths to advancing to first-in-human approaches for genome editing in vivo; (5) the facilitation of manufacturing of the editing machinery and the resulting drug product; and (6) the expansion of the scope of clinical applications both to common disease (e.g., chronic pain and cardiovascular disease) and ultrarare genetic conditions. The upcoming special issue will feature high profile review articles and solicited research articles from leaders in the fields of genome editing and clinical translation, including Drs. David Liu, Paula Cannon, Crystal Mackall, Fyodor Urnov, Katherine High, Mitchell Weiss, Daniel Bauer, Nicole Gaudelli, and Hans-Peter Kiem, among others. Interested authors of potential contributions to this special issue are encouraged to submit proposals to the editors at [email protected] for speedy consideration. The editors also encourage the submission of relevant Editorials, Commentaries, and other opinion pieces for consideration. Stay tuned for the Cell Press “Call for papers,” which will include the full list of solicited contributions for this exciting project! The target date for original research article submissions is no later than November 30, 2020.