Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency
Open accessAbstract
It has been 9 years since Mr. Jesse Gelsinger died from complications of vector administration in a liver gene therapy trial of research subjects with a deficiency of ornithine transcarbamylase (OTCD). This study was performed at the Institute for Human Gene Therapy of the University of Pennsylvania (Penn) which I directed. His tragic death provoked a series of events that had implications beyond those directly involved in the clinical trial. The events surrounding the death of this research subject have been the topic of much coverage and commentary in the popular press. The goal of this article is to share with you my reflections on the OTCD gene therapy trial and lessons that I have learned which may be of value to others engaged in various aspects of translational medicine.
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Adenoviral vectors have broader tropism, can be grown as high-titer recombinant viruses present in an episomal state, and can transduce dividing and non-dividing cells.
“Ads are an attractive delivery system because of their broader tropism, grown as high-titer recombinant viruses present in an episomal state, and their ability to transduce dividing and non-dividing cells [55].”
From The Ocular Gene Delivery Landscape (2021) · cites this paper as [55]
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Self-citationCurrent topic: Ornithine carbamoyltransferase deficiency
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- Authors
- Wilson, J. M.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Wilson, James M.
- ORCID
- Wilson, James M.
- Venue
- Molecular Genetics and Metabolism
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 96
- Issue
- 4
- Pages
- 151-157
- ISSN
- 1096-7192 (ISSN-L)
- OpenAlex
- W2107496779
- Cited by
- 299
- References
- 21
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 12 · 2023: 18 · 2022: 23 · 2021: 23 · 2020: 17 · 2019: 21 · 2018: 20 · 2017: 25 · 2016: 19 · 2015: 23 · 2014: 13 · 2013: 14 · 2012: 15
- FWCI
- 7.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Genetics and Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
- Health Sciences › Medicine › Physiology › Biomedical Ethics and Regulation
- Keywords
- ornithine transcarbamylase deficiency, gene therapy, Jesse Gelsinger, clinical trial safety, translational medicine, lessons learned, research ethics
- MeSH terms
- Clinical Trials as Topic, Humans, Genetic Therapy, Clinical Trials, Phase I as Topic, Ornithine Carbamoyltransferase Deficiency Disease
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