ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
Stable human FIX expression after 0.9G intrauterine gene transfer of self-complementary adeno-associated viral vector 5 and 8 in macaques.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 73 citations in OpenAlex.
- Evaluation of Maternal Safety Following Prenatal Cell and Gene Therapy for Hemophilia A.Prenatal diagnosis · 2026Article
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- Transabdominal ultrasound guided AAV9-GFP delivery in fetal pigs: a translational and minimally invasive model for in utero fetal gene therapy.Gene therapy · 2025Article
- Sustained high expression of human FVII following AAV8-mediated gene delivery in mice.Molecular therapy. Methods & clinical development · 2025Article
- In utero therapy for spinal muscular atrophy: closer to clinical translation.Brain : a journal of neurology · 2025Review
- Hemophilia A: An Ideal Disease for Prenatal Therapy.Prenatal diagnosis · 2025Review
- Transformative approaches in hemophilia management: from traditional therapies to prenatal stem cell treatment.Frontiers in bioengineering and biotechnology · 2025Review
- Fetal gene therapy.Journal of inherited metabolic disease · 2024Review
- In Utero Cell Treatment of Hemophilia A Mice via Human Amniotic Fluid Mesenchymal Stromal Cell Engraftment.International journal of molecular sciences · 2023Article
- Lack of germline transmission in male mice following a single intravenous administration of AAV5-hFVIII-SQ gene therapy.Gene therapy · 2023Article
- Acceptability of prenatal diagnosis and prenatal treatment of haemophilia using cell and gene therapies within US haemophilia community.Haemophilia : the official journal of the World Federation of Hemophilia · 2023Article
- Gene modification therapies for hereditary diseases in the fetus.Prenatal diagnosis · 2023Review
- Influence of Immune System Abnormalities Caused by Maternal Immune Activation in the Postnatal Period.Cells · 2023Review
- Prenatal Somatic Cell Gene Therapies: Charting a Path Toward Clinical Applications (Proceedings of the CERSI-FDA Meeting).Journal of clinical pharmacology · 2022Review
- Evaluating the state of the science for adeno-associated virus integration: An integrated perspective.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Article
- A narrative review of in utero gene therapy: advances, challenges, and future considerations.Translational pediatrics · 2021Review
- Liver-Targeted AAV8 Gene Therapy Ameliorates Skeletal and Cardiovascular Pathology in a Mucopolysaccharidosis IVA Murine Model.Molecular therapy. Methods & clinical development · 2020Article
- Fetal Gene Therapy Using a Single Injection of Recombinant AAV9 Rescued SMA Phenotype in Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- In Utero Gene Therapy (IUGT) Using GLOBE Lentiviral Vector Phenotypically Corrects the Heterozygous Humanised Mouse Model and Its Progress Can Be Monitored Using MRI Techniques.Scientific reports · 2019Article
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Authors and funding
20 authors at 8 institutions in 5 countries.
Funding
Abstract
Intrauterine gene transfer (IUGT) offers ontological advantages including immune naiveté mediating tolerance to the vector and transgenic products, and effecting a cure before development of irreversible pathology. Despite proof-of-principle in rodent models, expression efficacy with a therapeutic transgene has yet to be demonstrated in a preclinical nonhuman primate (NHP) model. We aimed to determine the efficacy of human Factor IX (hFIX) expression after adeno-associated-viral (AAV)-mediated IUGT in NHP. We injected 1.0-1.95 × 10(13) vector genomes (vg)/kg of self-complementary (sc) AAV5 and 8 with a LP1-driven hFIX transgene intravenously in 0.9G late gestation NHP fetuses, leading to widespread transduction with liver tropism. Liver-specific hFIX expression was stably maintained between 8 and 112% of normal activity in injected offspring followed up for 2-22 months. AAV8 induced higher hFIX expression (P = 0.005) and milder immune response than AAV5. Random hepatocellular integration was found with no hotspots. Transplacental spread led to low-level maternal tissue transduction, without evidence of immunotoxicity or germline transduction in maternal oocytes. A single intravenous injection of scAAV-LP1-hFIXco to NHP fetuses in late-gestation produced sustained clinically-relevant levels of hFIX with liver-specific expression and a non-neutralizing immune response. These data are encouraging for conditions where gene transfer has the potential to avert perinatal death and long-term irreversible sequelae.
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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.