FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1541053001> ?p ?o ?g. }

• W1541053001 endingPage "100" @default.
• W1541053001 startingPage "91" @default.
• W1541053001 abstract "Abstract The high risk of insertional oncogenesis reported in clinical trials using integrating retroviral vectors to genetically modify hematopoietic stem and progenitor cells (HSPCs) requires the development of safety strategies to minimize risks associated with novel cell and gene therapies. The ability to ablate genetically modified cells in vivo is desirable, should an abnormal clone emerge. Inclusion of “suicide genes” in vectors to facilitate targeted ablation of vector-containing abnormal clones in vivo is one potential safety approach. We tested whether the inclusion of the “inducible Caspase-9” (iCasp9) suicide gene in a gamma-retroviral vector facilitated efficient elimination of vector-containing HSPCs and their hematopoietic progeny in vivo long-term, in an autologous non-human primate transplantation model. Following stable engraftment of iCasp9 expressing hematopoietic cells in rhesus macaques, administration of AP1903, a chemical inducer of dimerization able to activate iCasp9, specifically eliminated vector-containing cells in all hematopoietic lineages long-term, suggesting activity at the HSPC level. Between 75% and 94% of vector-containing cells were eliminated by well-tolerated AP1903 dosing, but lack of complete ablation was linked to lower iCasp9 expression in residual cells. Further investigation of resistance mechanisms demonstrated upregulation of Bcl-2 in hematopoietic cell lines transduced with the vector and resistant to AP1903 ablation. These results demonstrate both the potential and the limitations of safety approaches using iCasp9 to HSPC-targeted gene therapy settings, in a model with great relevance to clinical development. Stem Cells 2015;33:91–100" @default.
• W1541053001 created "2016-06-24" @default.
• W1541053001 creator A5000749752 @default.
• W1541053001 creator A5001523714 @default.
• W1541053001 creator A5004581558 @default.
• W1541053001 creator A5006433618 @default.
• W1541053001 creator A5017909971 @default.
• W1541053001 creator A5031734294 @default.
• W1541053001 creator A5060936416 @default.
• W1541053001 creator A5072719085 @default.
• W1541053001 creator A5075578073 @default.
• W1541053001 creator A5085389087 @default.
• W1541053001 date "2014-12-18" @default.
• W1541053001 modified "2023-10-14" @default.
• W1541053001 title "Regulated Apoptosis of Genetically Modified Hematopoietic Stem and Progenitor Cells Via an Inducible Caspase-9 Suicide Gene in Rhesus Macaques" @default.
• W1541053001 cites W1966530560 @default.
• W1541053001 cites W1966983163 @default.
• W1541053001 cites W1970182792 @default.
• W1541053001 cites W1982192987 @default.
• W1541053001 cites W1992947808 @default.
• W1541053001 cites W1998609613 @default.
• W1541053001 cites W2017598005 @default.
• W1541053001 cites W2020455526 @default.
• W1541053001 cites W2029852810 @default.
• W1541053001 cites W2041165273 @default.
• W1541053001 cites W2056896498 @default.
• W1541053001 cites W2057879405 @default.
• W1541053001 cites W2061645642 @default.
• W1541053001 cites W2067016959 @default.
• W1541053001 cites W2082607509 @default.
• W1541053001 cites W2097175022 @default.
• W1541053001 cites W2099694564 @default.
• W1541053001 cites W2102859148 @default.
• W1541053001 cites W2107046588 @default.
• W1541053001 cites W2111586718 @default.
• W1541053001 cites W2112041130 @default.
• W1541053001 cites W2122465970 @default.
• W1541053001 cites W2136274459 @default.
• W1541053001 cites W2137440275 @default.
• W1541053001 cites W2143693981 @default.
• W1541053001 cites W2152943305 @default.
• W1541053001 cites W2157402532 @default.
• W1541053001 doi "https://doi.org/10.1002/stem.1869" @default.
• W1541053001 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4270878" @default.
• W1541053001 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25330775" @default.
• W1541053001 hasPublicationYear "2014" @default.
• W1541053001 type Work @default.
• W1541053001 sameAs 1541053001 @default.
• W1541053001 citedByCount "28" @default.
• W1541053001 countsByYear W15410530012015 @default.
• W1541053001 countsByYear W15410530012016 @default.
• W1541053001 countsByYear W15410530012017 @default.
• W1541053001 countsByYear W15410530012018 @default.
• W1541053001 countsByYear W15410530012019 @default.
• W1541053001 countsByYear W15410530012020 @default.
• W1541053001 countsByYear W15410530012021 @default.
• W1541053001 countsByYear W15410530012022 @default.
• W1541053001 countsByYear W15410530012023 @default.
• W1541053001 crossrefType "journal-article" @default.
• W1541053001 hasAuthorship W1541053001A5000749752 @default.
• W1541053001 hasAuthorship W1541053001A5001523714 @default.
• W1541053001 hasAuthorship W1541053001A5004581558 @default.
• W1541053001 hasAuthorship W1541053001A5006433618 @default.
• W1541053001 hasAuthorship W1541053001A5017909971 @default.
• W1541053001 hasAuthorship W1541053001A5031734294 @default.
• W1541053001 hasAuthorship W1541053001A5060936416 @default.
• W1541053001 hasAuthorship W1541053001A5072719085 @default.
• W1541053001 hasAuthorship W1541053001A5075578073 @default.
• W1541053001 hasAuthorship W1541053001A5085389087 @default.
• W1541053001 hasBestOaLocation W15410530011 @default.
• W1541053001 hasConcept C104317684 @default.
• W1541053001 hasConcept C109159458 @default.
• W1541053001 hasConcept C111599444 @default.
• W1541053001 hasConcept C201750760 @default.
• W1541053001 hasConcept C203014093 @default.
• W1541053001 hasConcept C2778086970 @default.
• W1541053001 hasConcept C28328180 @default.
• W1541053001 hasConcept C32470452 @default.
• W1541053001 hasConcept C34981463 @default.
• W1541053001 hasConcept C40767141 @default.
• W1541053001 hasConcept C502942594 @default.
• W1541053001 hasConcept C54355233 @default.
• W1541053001 hasConcept C81089528 @default.
• W1541053001 hasConcept C86803240 @default.
• W1541053001 hasConcept C95444343 @default.
• W1541053001 hasConceptScore W1541053001C104317684 @default.
• W1541053001 hasConceptScore W1541053001C109159458 @default.
• W1541053001 hasConceptScore W1541053001C111599444 @default.
• W1541053001 hasConceptScore W1541053001C201750760 @default.
• W1541053001 hasConceptScore W1541053001C203014093 @default.
• W1541053001 hasConceptScore W1541053001C2778086970 @default.
• W1541053001 hasConceptScore W1541053001C28328180 @default.
• W1541053001 hasConceptScore W1541053001C32470452 @default.
• W1541053001 hasConceptScore W1541053001C34981463 @default.
• W1541053001 hasConceptScore W1541053001C40767141 @default.
• W1541053001 hasConceptScore W1541053001C502942594 @default.
• W1541053001 hasConceptScore W1541053001C54355233 @default.
• W1541053001 hasConceptScore W1541053001C81089528 @default.

• next