Ethical, Legal, and Social Issues (ELSI) in Human Somatic Gene Therapy Clinical Research: A Scoping Review

Dozens of gene therapies (GTs) have received regulatory approval, and hundreds more are in various research phases. To characterize the ethical, legal, and social implications (ELSI) associated with the clinical development of this relatively new therapeutic class, we conducted a scoping review of the literature. Articles were eligible if they were written in English and discussed ELSI in the context of human somatic GT clinical research. 273 articles published from 2013 to 2024 met the eligibility criteria. To characterize and synthesize the ELSI associated with human somatic GT clinical research, thematic analysis was performed on extracted ELSI-relevant text from 179 articles published between 2019 and early 2024, including reviews, empirical research articles, opinions/commentaries, reports, news articles, and blog posts. Twenty-four themes were identified, leading to the generation of five high-level themes: (1) assessment of the risks and benefits of GTs is scientifically and ethically challenging, (2) communication and engagement with the patient community is crucial, (3) access and justice issues are heightened, (4) ethical GT trial design requires thoughtful consideration, and (5) strategic decision-making about GT research has ethical implications and is impacted by financial considerations and the regulatory context. Potential approaches to the identified ELSI are explored and discussed.