ArticleMolecular pharmaceutics2019
Molecular Engineering of Adeno-Associated Virus Capsid Improves Its Therapeutic Gene Transfer in Murine Models of Hemophilia and Retinal Degeneration.
Article in Molecular pharmaceutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 31 citations in OpenAlex.
- Cancer cell-selective ectopic expression of CD20 as an antigen enables rituximab repurposing for solid tumour immunotherapy.Clinical and translational medicine · 2026Article
- Bioengineered AAV9 and Optimised Microdystrophin Vectors Augment Phenotypic Rescue in a Murine Model of Duchenne Muscular Dystrophy.Journal of cellular and molecular medicine · 2026Article
- Elucidating the genetic landscape of inherited retinal disorders in India.Human genomics · 2026Review
- Suppressing microtubule detyrosination augments adeno-associated virus 2 endosomal escape and gene delivery.Journal of cell science · 2025Article
- Analytical dissection of minor glycoforms and glycoprotein associations in rAAV preparations by multimodal glycoproteomics.Analytical and bioanalytical chemistry · 2025Article
- Emerging biotechnologies for engineering liver organoids.Bioactive materials · 2025Review
- Immune responses in retinal gene therapy: challenges, mechanisms, and future strategies.Frontiers in immunology · 2025Review
- Development of an Optimized Promoter System for Exosomal and Naked AAV Vector-Based Suicide Gene Therapy in Hepatocellular Carcinoma.ACS omega · 2024Article
- Glycosylation of recombinant adeno-associated virus serotype 6.Molecular therapy. Methods & clinical development · 2024Article
- AAV mediated repression of Neat1 lncRNA combined with F8 gene augmentation mitigates pathological mediators of joint disease in haemophilia.Journal of cellular and molecular medicine · 2024Article
- Hemophilia Healing with AAV: Navigating the Frontier of Gene Therapy.Current gene therapy · 2024Review
- Recent developments in gene therapy research in India.Journal of biosciences · 2024Review
- Glycosylation shapes the efficacy and safety of diverse protein, gene and cell therapies.Biotechnology advances · 2023Review
- Gene Therapy Approaches for the Treatment of Hemophilia B.International journal of molecular sciences · 2023Review
- Rational engineering of adeno-associated virus capsid enhances human hepatocyte tropism and reduces immunogenicity.Cell proliferation · 2022Article
- Directed evolution of adeno-associated virus 5 capsid enables specific liver tropism.Molecular therapy. Nucleic acids · 2022Article
- Astrocyte Reprogramming in Stroke: Opportunities and Challenges.Frontiers in aging neuroscience · 2022Review
- Advances in designing Adeno-associated viral vectors for development of anti-HBV gene therapeutics.Virology journal · 2021Review
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Recombinant adeno-associated virus (AAV)-based gene therapy has been promising, but several host-related transduction or immune challenges remain. For this mode of therapy to be widely applicable, it is crucial to develop high transduction and permeating vectors that infect the target at significantly low doses. Because glycosylation of capsid proteins is known to be rate limiting in the life cycle of many viruses, we reasoned that perturbation of glycosylation sites in AAV2 capsid will enhance gene delivery. In our first set experiments, pharmacological modulation of the glycosylation status in host cells, modestly decreased (1-fold) AAV2 packaging efficacy while it improved their gene expression (∼74%) in vitro. We then generated 24 mutant AAV2 vectors modified to potentially create or disrupt a glycosylation site in its capsid. Three of them demonstrated a 1.3-2.5-fold increase in transgene expression in multiple cell lines (HeLa, Huh7, and ARPE-19). Hepatic gene transfer of these vectors in hemophilia B mice, resulted in a 2-fold increase in human coagulation factor (F)IX levels, while its T/B-cell immunogenic response was unaltered. Subsequently, intravitreal gene transfer of glycosylation site-modified vectors in C57BL6/J mice demonstrated an increase in green fluorescence protein expression (∼2- to 4-fold) and enhanced permeation across retina. Subretinal administration of these modified vectors containing RPE65 gene further rescued the photoreceptor response in a murine model of Leber congenital amarousis. Our studies highlight the translational potential of glycosylation site-modified AAV2 vectors for hepatic and ocular gene therapy applications.
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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.