ArticleThe New England journal of medicine2014
Long-term safety and efficacy of factor IX gene therapy in hemophilia B.
Article in The New England journal of medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 735 papers, 4 of them syntheses that pooled it.
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.
An Open Label Dose-Escalation Study Of A Self Complementary Adeno-Associated Viral Vector (scAAV 2/8-LP1-hFIXco) For Gene Transfer in Hemophilia B
A Prospective, Single-center, Open-arm, Single-arm Study of the Safety and Preliminary Efficacy of Single Intravenous Infusion Administration of LY-M001 Injection in the Treatment of Adult Patients With Gaucher Disease Type I
Who cites it
735 citing papers in PubMed, 4 syntheses or guidelines pooled it, 1,240 citations in OpenAlex.
- Adeno-associated virus-based gene therapy for hemophilia A and B: a systematic review and meta-analysis.Blood advances · 2024Pooled it
- A systematic review of immunosuppressive protocols used in AAV gene therapy for monogenic disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Pooled it
- Gene therapy for people with hepatocellular carcinoma.The Cochrane database of systematic reviews · 2024Pooled it
- Changing trends in the development of AAV-based gene therapies: a meta-analysis of past and present therapies.Gene therapy · 2023Pooled it
- Completion of phase 2b trial of etranacogene dezaparvovec gene therapy in patients with hemophilia B over 5 years.Blood advances · 2025Trial
- Gene therapy for hemophilia B: results from the phase 1/2 101HEMB01/02 studies.Blood advances · 2025Trial
- Safety and Efficacy of DTX401, an AAV8-Mediated Liver-Directed Gene Therapy, in Adults With Glycogen Storage Disease Type I a (GSDIa).Journal of inherited metabolic disease · 2025Trial
- Clinical immunogenicity outcomes from GENEr8-1, a phase 3 study of valoctocogene roxaparvovec, an AAV5-vectored gene therapy for hemophilia A.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Trial
- Clinical immunogenicity in rAAV gene therapy: Insights and implications.Molecular therapy. Advances · 2026Review
- Rapamycin nanoparticles mitigate anti-AAV antibody formation in a mouse model of ornithine transcarbamylase deficiency.Molecular therapy. Advances · 2026Article
- Increased gene therapy efficacy through the use of extended half-life clotting factors.Blood advances · 2026Article
- Adeno-Associated virus-based approaches for mitochondrial diseases: advances and challenges.Molecular psychiatry · 2026Review
- The future of pediatric gene therapy: CRISPR-Cas9, AI, and personalized medicine.Pediatric research · 2026Review
- Reprogramming innate immunity through viral interference: A double-edged strategy for enhancing and containing gene therapies.Molecular therapy. Nucleic acids · 2026Review
- Adeno-associated virus-induced neurotoxicity is prevented by CpG depletion.Molecular therapy. Advances · 2026Article
- Consequences of human genetic variations inMolecular therapy. Advances · 2026Article
- AAV gene therapy for homozygous familial hypercholesterolemia: a phase 1 trial.Nature medicine · 2026Article
- Safety of Adeno-Associated Viral Vectors in Gene Therapy: Mechanisms of Toxicity, Clinical Risks, and Strategies for Their Minimization.International journal of molecular sciences · 2026Review
- Development of a tetracycline-inducible programmed ribosomal frameshifting platform for sensitive regulation of mammalian gene expression.Nucleic acids research · 2026Article
- Liver Gene Therapy in Fabry Disease Mice With Low Doses of rAAV2/8 Expressing a Codon-Optimized hGLA cDNA Results in Long-Term Disease Correction.Journal of inherited metabolic disease · 2026Article
675 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 12 institutions in 5 countries.
Funding
Abstract
backgroundIn patients with severe hemophilia B, gene therapy that is mediated by a novel self-complementary adeno-associated virus serotype 8 (AAV8) vector has been shown to raise factor IX levels for periods of up to 16 months. We wanted to determine the durability of transgene expression, the vector dose-response relationship, and the level of persistent or late toxicity.
methodsWe evaluated the stability of transgene expression and long-term safety in 10 patients with severe hemophilia B: 6 patients who had been enrolled in an initial phase 1 dose-escalation trial, with 2 patients each receiving a low, intermediate, or high dose, and 4 additional patients who received the high dose (2×10(12) vector genomes per kilogram of body weight). The patients subsequently underwent extensive clinical and laboratory monitoring.
resultsA single intravenous infusion of vector in all 10 patients with severe hemophilia B resulted in a dose-dependent increase in circulating factor IX to a level that was 1 to 6% of the normal value over a median period of 3.2 years, with observation ongoing. In the high-dose group, a consistent increase in the factor IX level to a mean (±SD) of 5.1±1.7% was observed in all 6 patients, which resulted in a reduction of more than 90% in both bleeding episodes and the use of prophylactic factor IX concentrate. A transient increase in the mean alanine aminotransferase level to 86 IU per liter (range, 36 to 202) occurred between week 7 and week 10 in 4 of the 6 patients in the high-dose group but resolved over a median of 5 days (range, 2 to 35) after prednisolone treatment.
conclusionsIn 10 patients with severe hemophilia B, the infusion of a single dose of AAV8 vector resulted in long-term therapeutic factor IX expression associated with clinical improvement. With a follow-up period of up to 3 years, no late toxic effects from the therapy were reported. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00979238.).
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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.