ArticleCell proliferation2022
Rational engineering of adeno-associated virus capsid enhances human hepatocyte tropism and reduces immunogenicity.
Article in Cell proliferation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- 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
- Identification and Phylogenetic Characterisation of Novel Adeno-Associated Virus Capsids in Non-Human Primate Tissues.Cell proliferation · 2026Article
- In vivo CAR-T therapy: from molecular design to precision delivery.Journal of nanobiotechnology · 2026Review
- [Adeno-associated virus-mediated gene therapy for genetic epilepsy: prospects and challenges].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026Review
- Gene editing in cancer therapy: overcoming drug resistance and enhancing precision medicine.Cancer gene therapy · 2025Review
- Engineering a streamlined virus-like particle for programmable tissue-specific gene delivery.Nature communications · 2025Article
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
- Engineering pluripotent stem cells with synthetic biology for regenerative medicine.Medical review (2021) · 2024Review
- Rational engineering of adeno-associated virus capsid enhances human hepatocyte tropism and reduces immunogenicity.Cell proliferation · 2022Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
objectivesGene therapy based on recombinant adeno-associated viral (rAAV) vectors has been proved to be clinically effective for genetic diseases. However, there are still some limitations, including possible safety concerns for high dose delivery and a decreasing number of target patients caused by the high prevalence of pre-existing neutralizing antibodies, hindering its application. Herein, we explored whether there was an engineering strategy that can obtain mutants with enhanced transduction efficiency coupled with reduced immunogenicity.
methodsWe described a new strategy for AAV capsids engineering by combining alterations of N-linked glycosylation and the mutation of PLA2-like motif. With this combined strategy, we generated novel variants derived from AAV8 and AAVS3.
resultsThe variants mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines. Importantly, all the variants screened out showed lower sensitivity to neutralizing antibody in vitro and in vivo. Moreover, the in vivo antibody profiles of variants were different from their parental AAV capsids.
conclusionsOur work proposed a new combined engineering strategy and engineered two liver-tropic AAVs. We also obtained several AAV variants with a higher transduction efficiency and lower sensitivity of neutralizing antibodies. By expanding the gene delivery toolbox, these variants may further facilitate the success of AAV gene therapy.
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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.