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Ethical challenges for a new generation of early-phase pediatric gene therapy trials


After decades of setbacks, gene therapy (GT) is experiencing major breakthroughs. Five GTs have received US regulatory approval since 2017, and over 900 others are currently in development. Many of these GTs target rare pediatric diseases that are severely life-limiting, given a lack of effective treatments. As these GTs enter early-phase clinical trials, specific ethical challenges remain unresolved in three domains: evaluating risks and potential benefits, selecting participants fairly, and engaging with patient communities. Drawing on our experience as clinical investigators, basic scientists, and bioethicists involved in a first-in-human GT trial for an ultrarare pediatric disease, we analyze these ethical challenges and offer points to consider for future GT trials.

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Fig. 1: Ethical complexity in early-phase pediatric gene therapy (GT) trials.


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The authors thank the patients and families who have supported and participated in the GAN trial. They also thank Benjamin Berkman, Sara Chandros Hull, and David Wendler for feedback on earlier drafts of this paper, and members of the NIH Clinical Center Bioethics Consultation Service for their insights on the GAN trial. This work was supported by the US National Institutes of Health Intramural Research Program.

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Correspondence to Annette Rid.

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Iyer, A.A., Saade, D., Bharucha-Goebel, D. et al. Ethical challenges for a new generation of early-phase pediatric gene therapy trials. Genet Med 23, 2057–2066 (2021).

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