{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Han J"],"funding":["National Key Research and Development Program","The Strategic Priority Research Program of the Chinese Academy of Sciences","National Natural Science Foundation of China","CAS Project for Young Scientists in Basic Research","National Key Research and Development Program of China"],"pagination":["e13339"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9715358"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["55(12)"],"pubmed_abstract":["<h4>Objectives</h4>Gene 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.<h4>Methods</h4>We 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.<h4>Results</h4>The 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.<h4>Conclusions</h4>Our 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."],"journal":["Cell proliferation"],"pubmed_title":["Rational engineering of adeno-associated virus capsid enhances human hepatocyte tropism and reduces immunogenicity."],"pmcid":["PMC9715358"],"funding_grant_id":["2019YFA0110800","2018YFA0109701","XDA16030400","31621004","YSBR-012","2018YFA0107703"],"pubmed_authors":["Li W","Xu K","Guo L","Huang C","Zhou Q","Zhang J","Zhu L","Zhang Y","Han J","Sun X"],"additional_accession":[]},"is_claimable":false,"name":"Rational engineering of adeno-associated virus capsid enhances human hepatocyte tropism and reduces immunogenicity.","description":"<h4>Objectives</h4>Gene 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.<h4>Methods</h4>We 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.<h4>Results</h4>The 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.<h4>Conclusions</h4>Our 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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2025-04-26T12:32:03.885Z","creation":"2025-04-06T14:01:56.044Z"},"accession":"S-EPMC9715358","cross_references":{"pubmed":["36135100"],"doi":["10.1111/cpr.13339"]}}