ArticleMolecular therapy. Methods & clinical development2022
Prednisolone reduces the interferon response to AAV in cynomolgus macaques and may increase liver gene expression.
Article in Molecular therapy. Methods & clinical development, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Translational insights from nonclinical studies of AAV gene therapies for hemophilia: mechanisms underpinning variability and durability of gene expression.Therapeutic advances in hematology · 2026Review
- Review
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- Progress in skin gene therapy: From the inside and out.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- The combination of rAAV pseudo-lipid nanoparticle and triamcinolone acetonide enables multi-administration to liver.Molecular therapy. Methods & clinical development · 2025Article
- Characterization of a novel conditional knockout mouse model to assess efficacy of mRNA therapy in the context of severe OTC deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Gene Therapy for Inherited Liver Disease: To Add or to Edit.International journal of molecular sciences · 2024Review
- Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration.Nature biotechnology · 2024Article
- Adeno-associated virus as a delivery vector for gene therapy of human diseases.Signal transduction and targeted therapy · 2024Review
- Harnessing whole human liver ex situ normothermic perfusion for preclinical AAV vector evaluation.Nature communications · 2024Article
- Prednisolone and rapamycin reduce the plasma cell gene signature and may improve AAV gene therapy in cynomolgus macaques.Gene therapy · 2024Article
- Current landscape of cystic fibrosis gene therapy.Frontiers in pharmacology · 2024Review
- Liver injury in cynomolgus monkeys following intravenous and intrathecal scAAV9 gene therapy delivery.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Treatment and management for children with urea cycle disorder in chronic stage.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Article
- Immunosuppression reduces rAAV2.5T neutralizing antibodies that limit efficacy following repeat dosing to ferret lungs.Molecular therapy. Methods & clinical development · 2023Article
- Gene therapy for liver diseases - progress and challenges.Nature reviews. Gastroenterology & hepatology · 2023Review
- Novel Gene-Correction-Based Therapeutic Modalities for Monogenic Liver Disorders.Bioengineering (Basel, Switzerland) · 2022Review
- Pathogenic variants of ornithine transcarbamylase deficiency: Nation-wide study in Japan and literature review.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ornithine transcarbamylase deficiency is a rare X-linked genetic urea cycle disorder leading to episodes of acute hyperammonemia, adverse cognitive and neurological effects, hospitalizations, and in some cases death. DTX301, a non-replicating, recombinant self-complimentary adeno-associated virus vector serotype 8 (scAAV8)-encoding human ornithine transcarbamylase, is a promising gene therapy for ornithine transcarbamylase deficiency; however, the impact of sex and prophylactic immunosuppression on ornithine transcarbamylase gene therapy outcomes is not well characterized. This study sought to describe the impact of sex and immunosuppression in adult, sexually mature female and male cynomolgus macaques through day 140 after DTX301 administration. Four study groups (n = 3/group) were included: male non-immunosuppressed; male immunosuppressed; female non-immunosuppressed; and female immunosuppressed. DTX301 was well tolerated with and without immunosuppression; no notable differences were observed between female and male groups across outcome measures. Prednisolone-treated animals exhibited a trend toward greater vector genome and transgene expression, although the differences were not statistically significant. The hepatic interferon gene signature was significantly decreased in prednisolone-treated animals, and a significant inverse relationship was observed between interferon gene signature levels and hepatic vector DNA and transgene RNA. These observations were not sustained upon immunosuppression withdrawal. Further studies may determine whether the observed effect can be prolonged.
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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.