ArticleMolecular therapy. Methods & clinical development2024
B cell focused transient immune suppression protocol for efficient AAV readministration to the liver.
Article in Molecular therapy. Methods & clinical development, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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.
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Who cites it
20 citing papers in PubMed, 18 citations in OpenAlex.
- Gene therapy for hereditary hematological disorders: From clinical breakthroughs to future horizons.Molecular therapy. Nucleic acids · 2026Review
- Rapamycin nanoparticles mitigate anti-AAV antibody formation in a mouse model of ornithine transcarbamylase deficiency.Molecular therapy. Advances · 2026Article
- Cancer cell-selective ectopic expression of CD20 as an antigen enables rituximab repurposing for solid tumour immunotherapy.Clinical and translational medicine · 2026Article
- Transient prophylactic immunosuppression with abatacept or dasatinib prevents immune responses in AAV gene transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Preclinical pharmacology and toxicology study of an AAV8-tATP7B vector for Wilson's disease.Clinical and molecular hepatology · 2026Article
- Current Status of Clinical Gene Therapy for Hemophilia and Globin Disorders.Journal of blood medicine · 2026Review
- Mechanisms of and mitigating strategies for cellular immune responses to CRISPR-associated nucleases in genome editing therapy.Frontiers in medicine · 2026Review
- Emerging Technologies Tackling Adeno-Associated Viruses (AAV) Immunogenicity in Gene Therapy Applications.Pharmaceutics · 2025Review
- Efficient Scaling up EV-AAVs Production via Cellular Nanoporation for Familial Hypercholesterolaemia Therapy.Journal of extracellular vesicles · 2025Article
- Wild-type and engineered adeno-associated viral vectors produce comparable opsin expression and light-evoked responses in rat skeletal muscle.Molecular therapy. Methods & clinical development · 2025Article
- Nonclinical strategies and considerations to enable the redosing of gene therapies.Molecular therapy. Methods & clinical development · 2025Review
- Exploring AAV-Mediated Gene Therapy for Inner Ear Diseases: from Preclinical Success to Clinical Potential.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Use of CD19-targeted immune modulation to eradicate AAV-neutralizing antibodies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Emerging clinical applications of ADAR based RNA editing.Stem cells translational medicine · 2025Review
- Gene therapy for hemophilia - From basic science to first approvals of "one-and-done" therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Intracranial AAV administration dose-dependently recruits B cells to inhibit the AAV redosing.Molecular therapy. Methods & clinical development · 2025Article
- Gene Therapy for Inherited Liver Disease: To Add or to Edit.International journal of molecular sciences · 2024Review
- Chopping down antibodies for a good cause.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Innate Immune Sensing of Adeno-Associated Virus Vectors.Human gene therapy · 2024Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Adeno-associated virus (AAV) vectors are used for correcting multiple genetic disorders. Although the goal is to achieve lifelong correction with a single vector administration, the ability to redose would enable the extension of therapy in cases in which initial gene transfer is insufficient to achieve a lasting cure, episomal vector forms are lost in growing organs of pediatric patients, or transgene expression is diminished over time. However, AAV typically induces potent and long-lasting neutralizing antibodies (NAbs) against capsid that prevents re-administration. To prevent NAb formation in hepatic AAV8 gene transfer, we developed a transient B cell-targeting protocol using a combination of monoclonal Ab therapy against CD20 (for B cell depletion) and BAFF (to slow B cell repopulation). Initiation of immunosuppression before (rather than at the time of) vector administration and prolonged anti-BAFF treatment prevented immune responses against the transgene product and abrogated prolonged IgM formation. As a result, vector re-administration after immune reconstitution was highly effective. Interestingly, re-administration before the immune system had fully recovered achieved further elevated levels of transgene expression. Finally, this immunosuppression protocol reduced Ig-mediated AAV uptake by immune cell types with implications to reduce the risk of immunotoxicities in human gene therapy with AAV.
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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.