FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2566987341> ?p ?o ?g. }

• W2566987341 endingPage "S42" @default.
• W2566987341 startingPage "S42" @default.
• W2566987341 abstract "Although recombinant AAV3 serotype vectors were largely ignored previously, owing to their poor transduction efficiency in all cells and tissues examined, our initial observation of their selective tropism for human liver cancer cell lines and primary human hepatocytes (Mol Genet Metabol., 98: 289-299, 2009; Hum Gene Ther., 21: 1741-1747, 2010; Gene Ther., 19: 375-84, 2012), has led to renewed interest in this serotype, since AAV3 vectors and their variants have now proven to be extremely efficient in targeting human and non-human primate hepatocytes in vitro as well as in vivo (Mol Ther., 22: S2, 2014; Mol Ther., 22: S91, 2014; Nature, 506: 382-386, 2014; Hum Gene Ther., 25: 1023-1034, 2014). Previously, it wasreported that the combination of ITR8 with AAV8 capsids (AAV8/8) resulted in vectors that led to at least 2-fold increase in transgene expression in mouse liver, compared with AAV8 capsids pseudotyped with ITR2 (AAV2/8) vectors (Mol. Ther. 11: S156, 2005), and that the ITRs from AAV serotypes 1-6 were interchangeable when they are packaged into AAV8 capsids (AAV1/8 – AAV6/8), but played no role in transgene expression in murine hepatocytes in vivo (J. Virol., 80: 426-439, 2006). In our present studies, we wished to evaluate the relative contribution of the cis-acting ITR from AAV3 (ITR3), as well as the trans-acting Rep proteins from AAV3 (Rep3) in the recombinant AAV3 vector production and transduction. To this end, we utilized two helper plasmid: pAAVr2c3, which carries rep2 and cap3 genes and pAAVr3c3, which carries rep3 and cap3 genes. Plasmid transfection assays revealed that both AAV2 and AAV3 Rep proteins were expressed at similar levels in the presence of adenoviral helper genes. We also generated two sets of single-stranded AAV vector constructs carrying an expression cassette containing the EGFP reporter gene flanked by either ITR2 or ITR3. Plasmid transfections of the ITR2- or the ITR3-containing expression cassettes into cultured cells also revealed no difference in the extent of transgene expression. The combination of ITR3 and Rep3 resulted in ~5-fold higher rAAV3 vector titers, as determined by quantitative PCR assays. Next, purified viral stocks of AAV3 vectors were generated and designated as Rep2-ITR2 and Rep3-ITR3, respectively. Interestingly, the transduction efficiency of Rep3-ITR3 AAV3 vectors was ~4-fold higher than that of Rep2-ITR2 AAV3 vectors in a human hepatocellular carcinoma cell line, Huh7, under identical conditions. Additional studies are currently underway to evaluate the efficacy of the Rep2-ITR2 and Rep3-ITR3 vectors in a murine xenograft model in vivo. In summary, our studies document that the combined use of the AAV3 ITRs, AAV3 Rep proteins, and AAV3 capsids lead to the production of recombinant AAV3 vectors with higher titers and with higher transduction efficiency, and suggest that the use of homologous ITRs, Rep proteins, and capsids are similarly likely to be applicable to other AAV serotypes vectors for their optimal use in human gene therapy." @default.
• W2566987341 created "2017-01-06" @default.
• W2566987341 creator A5009668299 @default.
• W2566987341 creator A5014006564 @default.
• W2566987341 creator A5034749831 @default.
• W2566987341 creator A5039731976 @default.
• W2566987341 creator A5043406353 @default.
• W2566987341 creator A5056974995 @default.
• W2566987341 creator A5068400760 @default.
• W2566987341 creator A5081093203 @default.
• W2566987341 date "2015-05-01" @default.
• W2566987341 modified "2023-10-16" @default.
• W2566987341 title "101. Generation of Improved Recombinant AAV3 Serotype Vectors Using AAV3 ITRS and AAV3 REP Proteins" @default.
• W2566987341 doi "https://doi.org/10.1016/s1525-0016(16)33706-6" @default.
• W2566987341 hasPublicationYear "2015" @default.
• W2566987341 type Work @default.
• W2566987341 sameAs 2566987341 @default.
• W2566987341 citedByCount "0" @default.
• W2566987341 crossrefType "journal-article" @default.
• W2566987341 hasAuthorship W2566987341A5009668299 @default.
• W2566987341 hasAuthorship W2566987341A5014006564 @default.
• W2566987341 hasAuthorship W2566987341A5034749831 @default.
• W2566987341 hasAuthorship W2566987341A5039731976 @default.
• W2566987341 hasAuthorship W2566987341A5043406353 @default.
• W2566987341 hasAuthorship W2566987341A5056974995 @default.
• W2566987341 hasAuthorship W2566987341A5068400760 @default.
• W2566987341 hasAuthorship W2566987341A5081093203 @default.
• W2566987341 hasBestOaLocation W25669873411 @default.
• W2566987341 hasConcept C102230213 @default.
• W2566987341 hasConcept C104317684 @default.
• W2566987341 hasConcept C111599444 @default.
• W2566987341 hasConcept C135983454 @default.
• W2566987341 hasConcept C15152581 @default.
• W2566987341 hasConcept C153911025 @default.
• W2566987341 hasConcept C159047783 @default.
• W2566987341 hasConcept C202751555 @default.
• W2566987341 hasConcept C202878990 @default.
• W2566987341 hasConcept C207001950 @default.
• W2566987341 hasConcept C22744801 @default.
• W2566987341 hasConcept C2522874641 @default.
• W2566987341 hasConcept C33602714 @default.
• W2566987341 hasConcept C35693153 @default.
• W2566987341 hasConcept C40767141 @default.
• W2566987341 hasConcept C54355233 @default.
• W2566987341 hasConcept C55493867 @default.
• W2566987341 hasConcept C86803240 @default.
• W2566987341 hasConceptScore W2566987341C102230213 @default.
• W2566987341 hasConceptScore W2566987341C104317684 @default.
• W2566987341 hasConceptScore W2566987341C111599444 @default.
• W2566987341 hasConceptScore W2566987341C135983454 @default.
• W2566987341 hasConceptScore W2566987341C15152581 @default.
• W2566987341 hasConceptScore W2566987341C153911025 @default.
• W2566987341 hasConceptScore W2566987341C159047783 @default.
• W2566987341 hasConceptScore W2566987341C202751555 @default.
• W2566987341 hasConceptScore W2566987341C202878990 @default.
• W2566987341 hasConceptScore W2566987341C207001950 @default.
• W2566987341 hasConceptScore W2566987341C22744801 @default.
• W2566987341 hasConceptScore W2566987341C2522874641 @default.
• W2566987341 hasConceptScore W2566987341C33602714 @default.
• W2566987341 hasConceptScore W2566987341C35693153 @default.
• W2566987341 hasConceptScore W2566987341C40767141 @default.
• W2566987341 hasConceptScore W2566987341C54355233 @default.
• W2566987341 hasConceptScore W2566987341C55493867 @default.
• W2566987341 hasConceptScore W2566987341C86803240 @default.
• W2566987341 hasLocation W25669873411 @default.
• W2566987341 hasOpenAccess W2566987341 @default.
• W2566987341 hasPrimaryLocation W25669873411 @default.
• W2566987341 hasRelatedWork W1153412892 @default.
• W2566987341 hasRelatedWork W1981626292 @default.
• W2566987341 hasRelatedWork W1994284515 @default.
• W2566987341 hasRelatedWork W1996746326 @default.
• W2566987341 hasRelatedWork W2008207428 @default.
• W2566987341 hasRelatedWork W2074302783 @default.
• W2566987341 hasRelatedWork W2163708786 @default.
• W2566987341 hasRelatedWork W3004887743 @default.
• W2566987341 hasRelatedWork W3160441310 @default.
• W2566987341 hasRelatedWork W561146044 @default.
• W2566987341 hasVolume "23" @default.
• W2566987341 isParatext "false" @default.
• W2566987341 isRetracted "false" @default.
• W2566987341 magId "2566987341" @default.
• W2566987341 workType "article" @default.