ArticleProceedings of the National Academy of Sciences of the United States of America1999
Short-term correction of factor VIII deficiency in a murine model of hemophilia A after delivery of adenovirus murine factor VIII in utero.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 77 citations in OpenAlex.
- Transplanting FVIII/ET3-secreting cells in fetal sheep increases FVIII levels long-term without inducing immunity or toxicity.Nature communications · 2023Article
- Gene modification therapies for hereditary diseases in the fetus.Prenatal diagnosis · 2023Review
- Mechanistic Insights into Factor VIII Immune Tolerance Induction via Prenatal Cell Therapy in Hemophilia A.Current stem cell reports · 2019Article
- A constitutive knockout of murine carbamoyl phosphate synthetase 1 results in death with marked hyperglutaminemia and hyperammonemia.Journal of inherited metabolic disease · 2019Article
- Lipid nanoparticle-targeted mRNA therapy as a treatment for the inherited metabolic liver disorder arginase deficiency.Proceedings of the National Academy of Sciences of the United States of America · 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
- Long-term correction of hemophilia A mice following lentiviral mediated delivery of an optimized canine factor VIII gene.Gene therapy · 2017Article
- Transfer of Therapeutic Genes into Fetal Rhesus Monkeys Using Recombinant Adeno-Associated Type I Viral Vectors.Human gene therapy. Clinical development · 2016Article
- In utero stem cell transplantation and gene therapy: rationale, history, and recent advances toward clinical application.Molecular therapy. Methods & clinical development · 2016Review
- Augmentation of transgene-encoded protein after neonatal injection of adeno-associated virus improves hepatic copy number without immune responses.Pediatric research · 2015Article
- Liver-targeted gene therapy: Approaches and challenges.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2015Review
- Hemophilia A: an ideal disease to correct in utero.Frontiers in pharmacology · 2014Review
- 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
- Engineering Factor Viii for Hemophilia Gene Therapy.Journal of genetic syndromes & gene therapy · 2011Article
- Perinatal gene transfer to the liver.Current pharmaceutical design · 2011Review
- Clinical and molecular characterization of a re-established line of sheep exhibiting hemophilia A.Journal of thrombosis and haemostasis : JTH · 2010Article
- Article
- Short-term rescue of neonatal lethality in a mouse model of propionic acidemia by gene therapy.Human gene therapy · 2009Article
- Gene therapy to the kidney using viral vectors.Paediatriki · 2008Article
- Persistent expression of factor VIII in vivo following nonprimate lentiviral gene transfer.Blood · 2005Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Development of in utero gene transfer approaches may provide therapies for genetic disorders with perinatal morbidity. In hemophilia A, prenatal and postnatal bleeding may be catastrophic, and modest increments in factor VIII (FVIII) activity are therapeutic. We performed transuterine i.p. gene transfer at day 15 of gestation in a murine model of hemophilia A. Normal, carrier (X(H)X), and FVIII-deficient (X(H)Y and X(H)X(H)) fetuses injected with adenoviral vectors carrying luciferase or beta-galactosidase reporter genes showed high-level gene expression with 91% fetal survival. The live-born rates of normal and FVIII-deficient animals injected in utero with adenovirus murine FVIII (3.3 x 10(5) plaque-forming units) was 87%. FVIII activity in plasma was 50.7 +/- 10.5% of normal levels at day 2 of life, 7.2 +/- 2.2% by day 15 of life, and no longer detectable at day 21 of life in hemophilic animals. Injection of higher doses of murine FVIII adenovirus at embryonic day 15 produced supranormal levels of FVIII activity in the neonatal period. PCR analysis identified viral genomes primarily in the liver, intestine, and spleen, although adenoviral DNA was detected in distal tissues when higher doses of adenovirus were administered. These studies show that transuterine i.p. injection of adenoviral vectors produces therapeutic levels of circulating FVIII throughout the neonatal period. The future development of efficient and persisting vectors that produce long-term gene expression may allow for in utero correction of genetic diseases originating in the fetal liver, hematopoietic stem cells, as well as other tissues.
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