ArticleHuman gene therapy2009
Factors determining the risk of inadvertent retroviral transduction of male germ cells after in utero gene transfer in sheep.
Article in Human gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 35 citations in OpenAlex.
- Hemophilia A: An Ideal Disease for Prenatal Therapy.Prenatal diagnosis · 2025Review
- Prenatal gene editing for neurodevelopmental diseases: Ethical considerations.American journal of human genetics · 2025Review
- Fetal gene therapy.Journal of inherited metabolic disease · 2024Review
- Prenatal Somatic Cell Gene Therapies: Charting a Path Toward Clinical Applications (Proceedings of the CERSI-FDA Meeting).Journal of clinical pharmacology · 2022Review
- Catching Them Early: Framework Parameters and Progress for Prenatal and Childhood Application of Advanced Therapies.Pharmaceutics · 2022Review
- A narrative review of in utero gene therapy: advances, challenges, and future considerations.Translational pediatrics · 2021Review
- Mechanistic Insights into Factor VIII Immune Tolerance Induction via Prenatal Cell Therapy in Hemophilia A.Current stem cell reports · 2019Article
- In utero stem cell transplantation and gene therapy: rationale, history, and recent advances toward clinical application.Molecular therapy. Methods & clinical development · 2016Review
- Hemophilia A: an ideal disease to correct in utero.Frontiers in pharmacology · 2014Review
- Engraftment potential of adipose tissue-derived human mesenchymal stem cells after transplantation in the fetal rabbit.Stem cells and development · 2012Article
- Treatment of Hemophilia A in Utero and Postnatally using Sheep as a Model for Cell and Gene Delivery.Journal of genetic syndromes & gene therapy · 2012Article
- Expression levels of the PiT-2 receptor explain, in part, the gestational age-dependent alterations in transduction efficiency after in utero retroviral-mediated gene transfer.The journal of gene medicine · 2012Article
- The fetal respiratory system as target for antenatal therapy.Facts, views & vision in ObGyn · 2011Review
- Gene therapy: the promise of a permanent cure.North Carolina medical journalArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The possibility of permanent genetic changes to the germline is central to the bioethics of in utero gene therapy (IUGT) because of the concern of inadvertent potentially deleterious alterations to the gene pool. Despite presumed protection of the male germline due to early germ cell (GC) compartmentalization, we reported that GCs within the developing ovine testes are transduced at low levels after retrovirus-mediated IUGT, thus underscoring the need for a thorough understanding of GC development in clinically predictive models to determine the optimal time to perform IUGT and avoid germline modification. In the present studies, we used the fetal sheep model to analyze GCs for phenotype, location, proliferation, and incidence of transduction after IUGT at various fetal ages to learn when during development the nascent germline is likely to be at greatest risk of retrovirus-mediated alteration. Our studies show that although GCs were transduced at all injection ages, the levels of transduction varied by nearly 700-fold as a function of the age at transfer. After remaining largely quiescent as they migrated to/settled within nascent sex cords, GCs began active cycling before cord closure was complete, suggesting this is likely the point at which they would be most susceptible to retroviral transduction.Furthermore, we observed that compartmentalization of GCs continued into early postnatal life, suggesting the male germline may be vulnerable to low-level inadvertent retroviral vector modification throughout fetal life, but that this risk can be minimized by performing IUGT later in gestation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.