FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2533097147> ?p ?o ?g. }

• W2533097147 endingPage "121" @default.
• W2533097147 startingPage "110" @default.
• W2533097147 abstract "Essentials Factor (F) VIII is an inefficiently expressed protein. Furin deletion FVIII variants were purified and characterized using in vitro and in vivo assays. These minimally modified novel FVIII variants have enhanced function. These variants provide a strategy for increasing FVIII expression in hemophilia A gene therapy.Background The major challenge for developing gene-based therapies for hemophilia A is that human factor VIII (hFVIII) has intrinsic properties that result in inefficient biosynthesis. During intracellular processing, hFVIII is predominantly cleaved at a paired basic amino acid cleaving enzyme (PACE) or furin cleavage site to yield a heterodimer that is the major form of secreted protein. Previous studies with B-domain-deleted (BDD) canine FVIII and hFVIII-R1645H, both differing from hFVIII by a single amino acid at this site, suggested that these proteins are secreted mainly in a single polypeptide chain (SC) form and exhibit enhanced function. Objective We hypothesized that deletion(s) of the furin site modulates FVIII biology and may enhance its function. Methods A series of recombinant hFVIII-furin deletion variants were introduced into hFVIII-BDD [Δ1645, 1645-46(Δ2), 1645-47(Δ3), 1645-48(Δ4), or Δ1648] and characterized. Results In vitro, recombinant purified Δ3 and Δ4 were primarily SC and, interestingly, had 2-fold higher procoagulant activity compared with FVIII-BDD. In vivo, the variants also have improved hemostatic function. After adeno-associated viral (AAV) vector delivery, the expression of these variants is 2-4-fold higher than hFVIII-BDD. Protein challenges of each variant in mice tolerant to hFVIII-BDD showed no anti-FVIII immune response. Conclusions These data suggest that the furin deletion hFVIII variants are superior to hFVIII-BDD without increased immunogenicity. In the setting of gene-based therapeutics, these novel variants provide a unique strategy to increase FVIII expression, thus lowering the vector dose, a critical factor for hemophilia A gene therapy." @default.
• W2533097147 created "2016-10-28" @default.
• W2533097147 creator A5007360666 @default.
• W2533097147 creator A5015452205 @default.
• W2533097147 creator A5021505658 @default.
• W2533097147 creator A5027727697 @default.
• W2533097147 creator A5047366587 @default.
• W2533097147 creator A5069878653 @default.
• W2533097147 creator A5083116189 @default.
• W2533097147 creator A5083658192 @default.
• W2533097147 creator A5083674151 @default.
• W2533097147 date "2017-01-01" @default.
• W2533097147 modified "2023-10-15" @default.
• W2533097147 title "Novel factor VIII variants with a modified furin cleavage site improve the efficacy of gene therapy for hemophilia A" @default.
• W2533097147 cites W1497282221 @default.
• W2533097147 cites W1519546700 @default.
• W2533097147 cites W1521912671 @default.
• W2533097147 cites W1539413326 @default.
• W2533097147 cites W1540151595 @default.
• W2533097147 cites W1563019217 @default.
• W2533097147 cites W1564299213 @default.
• W2533097147 cites W1581671952 @default.
• W2533097147 cites W1595085358 @default.
• W2533097147 cites W1722864023 @default.
• W2533097147 cites W1964975805 @default.
• W2533097147 cites W1969271703 @default.
• W2533097147 cites W1976329054 @default.
• W2533097147 cites W1982605743 @default.
• W2533097147 cites W1982845146 @default.
• W2533097147 cites W1991453997 @default.
• W2533097147 cites W1992155962 @default.
• W2533097147 cites W1997614150 @default.
• W2533097147 cites W2005368084 @default.
• W2533097147 cites W2017793568 @default.
• W2533097147 cites W2022951493 @default.
• W2533097147 cites W2026854040 @default.
• W2533097147 cites W2037417109 @default.
• W2533097147 cites W2039928766 @default.
• W2533097147 cites W2043167814 @default.
• W2533097147 cites W2048246139 @default.
• W2533097147 cites W2058518705 @default.
• W2533097147 cites W2059988954 @default.
• W2533097147 cites W2065336178 @default.
• W2533097147 cites W2067691677 @default.
• W2533097147 cites W2077276585 @default.
• W2533097147 cites W2093662358 @default.
• W2533097147 cites W2096674194 @default.
• W2533097147 cites W2099598492 @default.
• W2533097147 cites W2108868109 @default.
• W2533097147 cites W2110881562 @default.
• W2533097147 cites W2139853957 @default.
• W2533097147 cites W2153867928 @default.
• W2533097147 cites W2155776487 @default.
• W2533097147 cites W2533097147 @default.
• W2533097147 cites W36673156 @default.
• W2533097147 doi "https://doi.org/10.1111/jth.13543" @default.
• W2533097147 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5280213" @default.
• W2533097147 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27749002" @default.
• W2533097147 hasPublicationYear "2017" @default.
• W2533097147 type Work @default.
• W2533097147 sameAs 2533097147 @default.
• W2533097147 citedByCount "33" @default.
• W2533097147 countsByYear W25330971472015 @default.
• W2533097147 countsByYear W25330971472017 @default.
• W2533097147 countsByYear W25330971472018 @default.
• W2533097147 countsByYear W25330971472019 @default.
• W2533097147 countsByYear W25330971472020 @default.
• W2533097147 countsByYear W25330971472021 @default.
• W2533097147 countsByYear W25330971472022 @default.
• W2533097147 countsByYear W25330971472023 @default.
• W2533097147 crossrefType "journal-article" @default.
• W2533097147 hasAuthorship W2533097147A5007360666 @default.
• W2533097147 hasAuthorship W2533097147A5015452205 @default.
• W2533097147 hasAuthorship W2533097147A5021505658 @default.
• W2533097147 hasAuthorship W2533097147A5027727697 @default.
• W2533097147 hasAuthorship W2533097147A5047366587 @default.
• W2533097147 hasAuthorship W2533097147A5069878653 @default.
• W2533097147 hasAuthorship W2533097147A5083116189 @default.
• W2533097147 hasAuthorship W2533097147A5083658192 @default.
• W2533097147 hasAuthorship W2533097147A5083674151 @default.
• W2533097147 hasBestOaLocation W25330971471 @default.
• W2533097147 hasConcept C104317684 @default.
• W2533097147 hasConcept C111599444 @default.
• W2533097147 hasConcept C151730666 @default.
• W2533097147 hasConcept C153911025 @default.
• W2533097147 hasConcept C159047783 @default.
• W2533097147 hasConcept C175156509 @default.
• W2533097147 hasConcept C181199279 @default.
• W2533097147 hasConcept C202751555 @default.
• W2533097147 hasConcept C207001950 @default.
• W2533097147 hasConcept C2777265534 @default.
• W2533097147 hasConcept C40767141 @default.
• W2533097147 hasConcept C43369102 @default.
• W2533097147 hasConcept C54355233 @default.
• W2533097147 hasConcept C55493867 @default.
• W2533097147 hasConcept C86803240 @default.
• W2533097147 hasConceptScore W2533097147C104317684 @default.
• W2533097147 hasConceptScore W2533097147C111599444 @default.

• next