FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1990441318> ?p ?o ?g. }

• W1990441318 endingPage "1916" @default.
• W1990441318 startingPage "1907" @default.
• W1990441318 abstract "Delivery of genes that are larger than the wild-type adeno-associated virus (AAV) 4,681 nucleotide genome is inefficient using AAV vectors. We previously demonstrated in vitro that concurrent proteasome inhibitor (PI) treatment improves transduction by AAV vectors encoding oversized transgenes. In this study, an AAV vector with a 5.6 kilobase (kb) factor VIII expression cassette was used to test the effect of an US Food and Drug Administration–approved PI (bortezomib) treatment concurrent with vector delivery in vivo. Intrahepatic vector delivery resulted in factor VIII expression that persisted for >1 year in hemophilia mice. Single-dose bortezomib given with AAV2 or AAV8 factor VIII vector enhanced expression on average ~600 and ~300%, respectively. Moreover, coadministration of AAV8.canineFVIII (1 × 1013 vg/kg) and bortezomib in hemophilia A dogs (n = 4) resulted in normalization of the whole blood clotting time (WBCT) and 90% reduction in hemorrhages for >32 months compared to untreated hemophilia A dogs (n = 3) or dogs administered vector alone (n = 3). Demonstration of long-term phenotypic correction of hemophilia A dogs with combination adjuvant bortezomib and AAV vector expressing the oversized transgene establishes preclinical studies that support testing in humans and provides a working paradigm to facilitate a significant expansion of therapeutic targets for human gene therapy. Delivery of genes that are larger than the wild-type adeno-associated virus (AAV) 4,681 nucleotide genome is inefficient using AAV vectors. We previously demonstrated in vitro that concurrent proteasome inhibitor (PI) treatment improves transduction by AAV vectors encoding oversized transgenes. In this study, an AAV vector with a 5.6 kilobase (kb) factor VIII expression cassette was used to test the effect of an US Food and Drug Administration–approved PI (bortezomib) treatment concurrent with vector delivery in vivo. Intrahepatic vector delivery resulted in factor VIII expression that persisted for >1 year in hemophilia mice. Single-dose bortezomib given with AAV2 or AAV8 factor VIII vector enhanced expression on average ~600 and ~300%, respectively. Moreover, coadministration of AAV8.canineFVIII (1 × 1013 vg/kg) and bortezomib in hemophilia A dogs (n = 4) resulted in normalization of the whole blood clotting time (WBCT) and 90% reduction in hemorrhages for >32 months compared to untreated hemophilia A dogs (n = 3) or dogs administered vector alone (n = 3). Demonstration of long-term phenotypic correction of hemophilia A dogs with combination adjuvant bortezomib and AAV vector expressing the oversized transgene establishes preclinical studies that support testing in humans and provides a working paradigm to facilitate a significant expansion of therapeutic targets for human gene therapy." @default.
• W1990441318 created "2016-06-24" @default.
• W1990441318 creator A5016603833 @default.
• W1990441318 creator A5020081853 @default.
• W1990441318 creator A5037532361 @default.
• W1990441318 creator A5043067497 @default.
• W1990441318 creator A5044065218 @default.
• W1990441318 creator A5047315422 @default.
• W1990441318 creator A5053864014 @default.
• W1990441318 creator A5062881503 @default.
• W1990441318 creator A5078803622 @default.
• W1990441318 creator A5090056434 @default.
• W1990441318 date "2010-11-01" @default.
• W1990441318 modified "2023-10-18" @default.
• W1990441318 title "Proteasome Inhibitors Enhance Gene Delivery by AAV Virus Vectors Expressing Large Genomes in Hemophilia Mouse and Dog Models: A Strategy for Broad Clinical Application" @default.
• W1990441318 cites W1255418244 @default.
• W1990441318 cites W1564486248 @default.
• W1990441318 cites W1964975805 @default.
• W1990441318 cites W1970138286 @default.
• W1990441318 cites W1974840861 @default.
• W1990441318 cites W1979659851 @default.
• W1990441318 cites W1980491559 @default.
• W1990441318 cites W1982346550 @default.
• W1990441318 cites W1985656844 @default.
• W1990441318 cites W1995793532 @default.
• W1990441318 cites W1997123094 @default.
• W1990441318 cites W2008744347 @default.
• W1990441318 cites W2029750163 @default.
• W1990441318 cites W2041157989 @default.
• W1990441318 cites W2044477424 @default.
• W1990441318 cites W2049442129 @default.
• W1990441318 cites W2051442157 @default.
• W1990441318 cites W2063056703 @default.
• W1990441318 cites W2066313345 @default.
• W1990441318 cites W2067695390 @default.
• W1990441318 cites W2069674599 @default.
• W1990441318 cites W2081562071 @default.
• W1990441318 cites W2083107653 @default.
• W1990441318 cites W2083333314 @default.
• W1990441318 cites W2084114153 @default.
• W1990441318 cites W2086651005 @default.
• W1990441318 cites W2087185853 @default.
• W1990441318 cites W2090289970 @default.
• W1990441318 cites W2091718181 @default.
• W1990441318 cites W2111051741 @default.
• W1990441318 cites W2113444875 @default.
• W1990441318 cites W2122236774 @default.
• W1990441318 cites W2133590829 @default.
• W1990441318 cites W2139865704 @default.
• W1990441318 cites W2142439096 @default.
• W1990441318 cites W2142798211 @default.
• W1990441318 cites W2143529139 @default.
• W1990441318 cites W2147576659 @default.
• W1990441318 cites W2153386394 @default.
• W1990441318 cites W2153867928 @default.
• W1990441318 cites W2155710930 @default.
• W1990441318 cites W2158417626 @default.
• W1990441318 cites W2165834277 @default.
• W1990441318 cites W2167498902 @default.
• W1990441318 cites W2417891395 @default.
• W1990441318 doi "https://doi.org/10.1038/mt.2010.170" @default.
• W1990441318 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2990516" @default.
• W1990441318 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20700109" @default.
• W1990441318 hasPublicationYear "2010" @default.
• W1990441318 type Work @default.
• W1990441318 sameAs 1990441318 @default.
• W1990441318 citedByCount "105" @default.
• W1990441318 countsByYear W19904413182012 @default.
• W1990441318 countsByYear W19904413182013 @default.
• W1990441318 countsByYear W19904413182014 @default.
• W1990441318 countsByYear W19904413182015 @default.
• W1990441318 countsByYear W19904413182016 @default.
• W1990441318 countsByYear W19904413182017 @default.
• W1990441318 countsByYear W19904413182018 @default.
• W1990441318 countsByYear W19904413182019 @default.
• W1990441318 countsByYear W19904413182020 @default.
• W1990441318 countsByYear W19904413182021 @default.
• W1990441318 countsByYear W19904413182022 @default.
• W1990441318 countsByYear W19904413182023 @default.
• W1990441318 crossrefType "journal-article" @default.
• W1990441318 hasAuthorship W1990441318A5016603833 @default.
• W1990441318 hasAuthorship W1990441318A5020081853 @default.
• W1990441318 hasAuthorship W1990441318A5037532361 @default.
• W1990441318 hasAuthorship W1990441318A5043067497 @default.
• W1990441318 hasAuthorship W1990441318A5044065218 @default.
• W1990441318 hasAuthorship W1990441318A5047315422 @default.
• W1990441318 hasAuthorship W1990441318A5053864014 @default.
• W1990441318 hasAuthorship W1990441318A5062881503 @default.
• W1990441318 hasAuthorship W1990441318A5078803622 @default.
• W1990441318 hasAuthorship W1990441318A5090056434 @default.
• W1990441318 hasBestOaLocation W19904413181 @default.
• W1990441318 hasConcept C102230213 @default.
• W1990441318 hasConcept C104317684 @default.
• W1990441318 hasConcept C111599444 @default.
• W1990441318 hasConcept C135983454 @default.
• W1990441318 hasConcept C15152581 @default.
• W1990441318 hasConcept C153911025 @default.
• W1990441318 hasConcept C159047783 @default.

• next