ArticleProceedings of the National Academy of Sciences of the United States of America2005
Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helper-dependent adenoviral vector.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 139 citations in OpenAlex.
- High-capacity adenoviral vector-mediated expression of an LDLR/transferrin chimeric protein in muscle reduces atherosclerosis in LdlrMolecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Review
- Strategies for Modifying Adenoviral Vectors for Gene Therapy.International journal of molecular sciences · 2024Review
- Models of bilirubin neurological damage: lessons learned and new challenges.Pediatric research · 2023Review
- VikAD, a Vika site-specific recombinase-based system for efficient and scalable helper-dependent adenovirus production.Molecular therapy. Methods & clinical development · 2022Article
- Potential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapy.Cell & bioscience · 2021Review
- Capsid and Genome Modification Strategies to Reduce the Immunogenicity of Adenoviral Vectors.International journal of molecular sciences · 2021Review
- Low efficacy of recombinant SV40 in Ugt1a1-/- mice with severe inherited hyperbilirubinemia.PloS one · 2021Article
- Recombinant Adenoviruses for Delivery of Therapeutics Following Spinal Cord Injury.Frontiers in pharmacology · 2021Review
- Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects.Journal of inherited metabolic disease · 2017Review
- Developmental, Genetic, Dietary, and Xenobiotic Influences on Neonatal Hyperbilirubinemia.Molecular pharmacology · 2017Review
- Adenoviral vector-based strategies against infectious disease and cancer.Human vaccines & immunotherapeutics · 2016Review
- Adenovirus-Vectored Broadly Neutralizing Antibodies Directed Against gp120 Prevent Human Immunodeficiency Virus Type 1 Acquisition in Humanized Mice.Human gene therapy · 2015Article
- Sustained inhibition of hepatitis B virus replication in vivo using RNAi-activating lentiviruses.Gene therapy · 2015Article
- Challenges and Prospects for Helper-Dependent Adenoviral Vector-Mediated Gene Therapy.Biomedicines · 2014Review
- In the rat liver, Adenoviral gene transfer efficiency is comparable to AAV.Gene therapy · 2014Article
- PEGylated helper-dependent adenoviral vector expressing human Apo A-I for gene therapy in LDLR-deficient mice.Gene therapy · 2013Article
- Transgene expression up to 7 years in nonhuman primates following hepatic transduction with helper-dependent adenoviral vectors.Human gene therapy · 2013Article
- The role of chromatin in adenoviral vector function.Viruses · 2013Review
- Differential type I interferon-dependent transgene silencing of helper-dependent adenoviral vs. adeno-associated viral vectors in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Crigler-Najjar syndrome is a recessively inherited disorder characterized by severe unconjugated hyperbilirubinemia caused by a deficiency of uridine diphospho-glucuronosyl transferase 1A1. Current therapy relies on phototherapy to prevent kernicterus, but liver transplantation presently is the only permanent cure. Gene therapy is a potential alternative, and recent work has shown that helper-dependent adenoviral (HD-Ad) vectors, devoid of all viral coding sequences, induce prolonged transgene expression and exhibit significantly less chronic toxicity than early-generation Ad vectors. We used a HD-Ad vector to achieve liver-restricted expression of human uridine diphospho-glucuronosyl transferase 1A1 in the Gunn rat, a model of the human disorder. Total plasma bilirubin levels were reduced from >5.0 mg/dl to <<1.4 mg/dl for >2 yr after a single i.v. administration of vector expressing the therapeutic transgene at a dose of 3 x 10(12) viral particles per kg. HPLC analysis of bile from treated rats showed the presence of bilirubin glucuronides at normal WT levels >2 yr after one injection of vector, and i.v. injection of bilirubins IIIalpha and XIIIalpha in the same animals revealed excess bilirubin-conjugating capacity. There was no significant elevation of liver enzymes (alanine aminotransferase) and only transient, moderate thrombocytopenia after injection of the vector. A clinically significant reduction in serum bilirubin was observed with a dose as low as 6 x 10(11) viral particles per kg. We conclude that complete, long-term correction of hyperbilirubinemia in the Gunn rat model of Crigler-Najjar syndrome can be achieved with one injection of HD-Ad vector and negligible chronic toxicity.
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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.