FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2071714774> ?p ?o ?g. }

• W2071714774 endingPage "1543" @default.
• W2071714774 startingPage "1527" @default.
• W2071714774 abstract "Adeno-associated virus 2 (AAV2) vectors transduce fibroblasts and mesenchymal stem cells (MSCs) inefficiently, which limits their potential widespread applicability in combinatorial gene and cell therapy. We have reported that AAV2 vectors fail to traffic efficiently to the nucleus in murine fibroblasts. We have also reported that site-directed mutagenesis of surface-exposed tyrosine residues on viral capsids leads to improved intracellular trafficking of the mutant vectors, and the transduction efficiency of the single tyrosine-mutant vectors is ∼10-fold higher in human cells. In the current studies, we evaluated the transduction efficiency of single as well as multiple tyrosine-mutant AAV2 vectors in murine fibroblasts. Our results indicate that the Y444F mutant vectors transduce these cells most efficiently among the seven single-mutant vectors, with >30-fold increase in transgene expression compared with the wild-type vectors. When the Y444F mutation is combined with additional mutations (Y500F and Y730F), the transduction efficiency of the triple-mutant vectors is increased by ∼130-fold and the viral intracellular trafficking is also significant improved. Similarly, the triple-mutant vectors are capable of transducing up to 80–90% of bone marrow-derived primary murine as well as human MSCs. Thus, high-efficiency transduction of fibroblasts with reprogramming genes to generate induced pluripotent stem cells, and the MSCs for delivering therapeutic genes, should now be feasible with the tyrosine-mutant AAV vectors. Fibroblasts and mesenchymal stem cells (MSCs) are promising targets for gene and cell therapy. Recombinant adeno-associated virus 2 (AAV2) vectors are currently in use in several Phase I/II clinical trials for gene therapy. However, the existing data show that AAV2 vector-mediated transduction of fibroblasts and MSCs is inefficient. We observed that AAV2 vectors containing mutations in three surface-exposed tyrosine residues significantly increase transduction efficiency in fibroblasts, as well as in both human and murine primary MSCs. The increased transduction efficiency of these triple-mutant AAV2 vectors correlates well with improved viral intracellular trafficking in fibroblasts. These data provide strong evidence that high-efficiency gene delivery and transgene expression by AAV vectors are indeed feasible, which should facilitate the generation of induced pluripotent stem cells, as well as the use of MSCs in combinatorial gene and cell therapy. Previous reports have shown that site-directed mutagenesis of surface-exposed tyrosine residues on the capsid of AAV2 leads to enhanced transduction efficiency. In this report, Li and colleagues use these AAV2 tyrosine mutants and demonstrate that they are capable of transducing up to 90% of mouse and human bone marrow derived mesenchymal stem cells." @default.
• W2071714774 created "2016-06-24" @default.
• W2071714774 creator A5023374471 @default.
• W2071714774 creator A5034749831 @default.
• W2071714774 creator A5055588771 @default.
• W2071714774 creator A5062581730 @default.
• W2071714774 creator A5062850183 @default.
• W2071714774 creator A5081093203 @default.
• W2071714774 creator A5085893176 @default.
• W2071714774 date "2010-11-01" @default.
• W2071714774 modified "2023-10-16" @default.
• W2071714774 title "High-Efficiency Transduction of Fibroblasts and Mesenchymal Stem Cells by Tyrosine-Mutant AAV2 Vectors for Their Potential Use in Cellular Therapy" @default.
• W2071714774 cites W126651838 @default.
• W2071714774 cites W1488961672 @default.
• W2071714774 cites W1519383882 @default.
• W2071714774 cites W1525995077 @default.
• W2071714774 cites W1597426364 @default.
• W2071714774 cites W1607201181 @default.
• W2071714774 cites W1681143022 @default.
• W2071714774 cites W1975528602 @default.
• W2071714774 cites W1988508537 @default.
• W2071714774 cites W1988911750 @default.
• W2071714774 cites W2002179012 @default.
• W2071714774 cites W2004356764 @default.
• W2071714774 cites W2010031978 @default.
• W2071714774 cites W2019418234 @default.
• W2071714774 cites W2019612944 @default.
• W2071714774 cites W2019713216 @default.
• W2071714774 cites W2022040013 @default.
• W2071714774 cites W2024617071 @default.
• W2071714774 cites W2025246242 @default.
• W2071714774 cites W2032570745 @default.
• W2071714774 cites W2040312123 @default.
• W2071714774 cites W2049340874 @default.
• W2071714774 cites W2049592320 @default.
• W2071714774 cites W2050689355 @default.
• W2071714774 cites W2051765359 @default.
• W2071714774 cites W2053952731 @default.
• W2071714774 cites W2054892900 @default.
• W2071714774 cites W2059202997 @default.
• W2071714774 cites W2060216304 @default.
• W2071714774 cites W2068868913 @default.
• W2071714774 cites W2070054006 @default.
• W2071714774 cites W2070252374 @default.
• W2071714774 cites W2084305053 @default.
• W2071714774 cites W2084894670 @default.
• W2071714774 cites W2101605345 @default.
• W2071714774 cites W2103904163 @default.
• W2071714774 cites W2104978512 @default.
• W2071714774 cites W2106326323 @default.
• W2071714774 cites W2111051741 @default.
• W2071714774 cites W2114741749 @default.
• W2071714774 cites W2122236774 @default.
• W2071714774 cites W2125987139 @default.
• W2071714774 cites W2128486910 @default.
• W2071714774 cites W2129283689 @default.
• W2071714774 cites W2130515212 @default.
• W2071714774 cites W2137222303 @default.
• W2071714774 cites W2137440275 @default.
• W2071714774 cites W2138951900 @default.
• W2071714774 cites W2138977668 @default.
• W2071714774 cites W2141482826 @default.
• W2071714774 cites W2141575938 @default.
• W2071714774 cites W2142046859 @default.
• W2071714774 cites W2143836588 @default.
• W2071714774 cites W2147032028 @default.
• W2071714774 cites W2151809142 @default.
• W2071714774 cites W2152187442 @default.
• W2071714774 cites W2156246988 @default.
• W2071714774 cites W2158417626 @default.
• W2071714774 cites W2162886054 @default.
• W2071714774 cites W2169181196 @default.
• W2071714774 cites W2177438840 @default.
• W2071714774 cites W2184444629 @default.
• W2071714774 cites W2418361432 @default.
• W2071714774 cites W4250016637 @default.
• W2071714774 cites W4253384929 @default.
• W2071714774 doi "https://doi.org/10.1089/hum.2010.005" @default.
• W2071714774 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2987376" @default.
• W2071714774 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20507237" @default.
• W2071714774 hasPublicationYear "2010" @default.
• W2071714774 type Work @default.
• W2071714774 sameAs 2071714774 @default.
• W2071714774 citedByCount "62" @default.
• W2071714774 countsByYear W20717147742012 @default.
• W2071714774 countsByYear W20717147742013 @default.
• W2071714774 countsByYear W20717147742014 @default.
• W2071714774 countsByYear W20717147742016 @default.
• W2071714774 countsByYear W20717147742017 @default.
• W2071714774 countsByYear W20717147742018 @default.
• W2071714774 countsByYear W20717147742019 @default.
• W2071714774 countsByYear W20717147742020 @default.
• W2071714774 countsByYear W20717147742021 @default.
• W2071714774 countsByYear W20717147742022 @default.
• W2071714774 crossrefType "journal-article" @default.
• W2071714774 hasAuthorship W2071714774A5023374471 @default.
• W2071714774 hasAuthorship W2071714774A5034749831 @default.
• W2071714774 hasAuthorship W2071714774A5055588771 @default.

• next