ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Development of Patient-specific AAV Vectors After Neutralizing Antibody Selection for Enhanced Muscle Gene Transfer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- Inner Ear Gene Therapy: An Overview from Bench to Bedside.Molecular diagnosis & therapy · 2025Review
- Understanding AAV vector immunogenicity: from particle to patient.Theranostics · 2024Review
- Structure-guided AAV capsid evolution strategies for enhanced CNS gene delivery.Nature protocols · 2023Review
- Article
- Mitigating Serious Adverse Events in Gene Therapy with AAV Vectors: Vector Dose and Immunosuppression.Drugs · 2023Review
- Multiplexing AAV Serotype-Specific Neutralizing Antibodies in Preclinical Animal Models and Humans.Biomedicines · 2023Article
- Semirational bioengineering of AAV vectors with increased potency and specificity for systemic gene therapy of muscle disorders.Science advances · 2022Article
- Red Blood Cell Anchoring Enables Targeted Transduction and Re-Administration of AAV-Mediated Gene Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Maybe you can turn me on: CRISPRa-based strategies for therapeutic applications.Cellular and molecular life sciences : CMLS · 2022Review
- Selective Anti-AAV Antibody Depletion by Hemapheresis and Immunoadsorption.Methods in molecular biology (Clifton, N.J.) · 2022Article
- A versatile toolkit for overcoming AAV immunity.Frontiers in immunology · 2022Review
- Overcoming the Challenges Imposed by Humoral Immunity to AAV Vectors to Achieve Safe and Efficient Gene Transfer in Seropositive Patients.Frontiers in immunology · 2022Review
- Article
- Adeno-Associated Viruses (AAV) and Host Immunity - A Race Between the Hare and the Hedgehog.Frontiers in immunology · 2021Review
- Of rAAV and Men: From Genetic Neuromuscular Disorder Efficacy and Toxicity Preclinical Studies to Clinical Trials and Back.Journal of personalized medicine · 2020Review
- AAV Vectored Immunoprophylaxis for Filovirus Infections.Tropical medicine and infectious disease · 2020Review
- Bound Protein- and Peptide-Based Strategies for Adeno-Associated Virus Vector-Mediated Gene Therapy: Where Do We Stand Now?Human gene therapy · 2020Article
- Modifiers of Adeno-Associated Virus-Mediated Gene Expression in Implication for Serotype-Universal Neutralizing Antibody Assay.Human gene therapy · 2020Article
- Rescuing AAV gene transfer from neutralizing antibodies with an IgG-degrading enzyme.JCI insight · 2020Article
- Development of AAV Variants with Human Hepatocyte Tropism and Neutralizing Antibody Escape Capacity.Molecular therapy. Methods & clinical development · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
A major hindrance in gene therapy trials with adeno-associated virus (AAV) vectors is the presence of neutralizing antibodies (NAbs) that inhibit AAV transduction. In this study, we used directed evolution techniques in vitro and in mouse muscle to select novel NAb escape AAV chimeric capsid mutants in the presence of individual patient serum. AAV mutants isolated in vitro escaped broad patient-specific NAb activity but had poor transduction ability in vivo. AAV mutants isolated in vivo had enhanced NAb evasion from cognate serum and had high muscle transduction ability. More importantly, structural modeling identified a 100 amino acid motif from AAV6 in variable region (VR) III that confers this enhanced muscle tropism. In addition, a predominantly AAV8 capsid beta barrel template with a specific preference for AAV1/AAV9 in VR VII located at threefold symmetry axis facilitates NAb escape. Our data strongly support that chimeric AAV capsids composed of modular and nonoverlapping domains from various serotypes are capable of evading patient-specific NAbs and have enhanced muscle transduction.
Indexed as
Identifiers
What OpenQuestion holds
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.