Matches in SemOpenAlex for { <https://semopenalex.org/work/W2553741326> ?p ?o ?g. }
Showing items 1 to 87 of
87
with 100 items per page.
- W2553741326 endingPage "4802" @default.
- W2553741326 startingPage "4802" @default.
- W2553741326 abstract "Abstract Background: Hematopoietic stem cell (HSC) transplantation remains the only clinically observed path to functional cure of HIV infection. To better understand the mechanism of HSC-driven HIV control, and apply this therapy to a greater number of patients, we have developed a model of combination antiretroviral therapy (cART)-suppressed HIV infection in the pigtailed macaque, applicable to both gene therapy- and allogeneic transplant-based cure strategies. Following transplantation of HIV-resistant, autologous cells into conditioned animals, we are evaluating the extent to which protected cell progeny impede infection by SIV/HIV (SHIV) chimeric virus in vivo. Methods: Animals are challenged with SHIV virus containing an HIV envelope, after which a 3-drug cART regimen is initiated. Autologous HSCs are engineered to resist infection through targeted disruption of the CCR5 genetic locus using Zinc Finger Nucleases (ZFNs). Engraftment, persistence, and SHIV response of these autologous stem cells, and stem cell-derived lymphoid and myeloid cells, are measured in vivo. Results: SHIV infection in the pigtailed macaque model results in sustained viremia with consequent reduction in CD4+ T cells. Moreover, administration of three-drug cART leads to rapid and durable suppression of plasma viremia to <30 copies/mL plasma - suggesting that this model recapitulates key features of HIV infection and treatment in humans. CCR5 targeting experiments yield up to 60% gene disruption in CD34+ cells ex vivo, translating to approximately 5% disruption in vivo following transplant. Importantly, up to 10% of transplanted cells carry two disrupted alleles of CCR5; these cells should preferentially reconstitute CD4+ T-cell pools and other susceptible subsets following SHIV challenge. Consistent with this prediction, our preliminary data suggest that CCR5-deleted cells undergo positive selection following SHIV challenge in vivo. Conclusions: Our pigtailed macaque model of HIV infection and cART represents a promising platform for modeling functional cure strategies. Here we show that CCR5 deletion does not impair HSC engraftment or differentiation, and that CCR5-deleted cells can undergo SHIV-dependent positive selection even when present at low levels. Our model enables the evaluation of novel therapeutic approaches in the clinically relevant context of cART controlled SHIV infection - a setting of particular importance to approaches aimed at addressing the viral reservoir. Disclosures Wang: Sangamo Biosciences: Employment. Holmes:Sangamo Biosciences: Employment. Gregory:Sangamo Biosciences: Employment." @default.
- W2553741326 created "2016-11-30" @default.
- W2553741326 creator A5001976406 @default.
- W2553741326 creator A5009781116 @default.
- W2553741326 creator A5032980660 @default.
- W2553741326 creator A5039265791 @default.
- W2553741326 creator A5055711908 @default.
- W2553741326 creator A5060993908 @default.
- W2553741326 creator A5073932029 @default.
- W2553741326 date "2014-12-06" @default.
- W2553741326 modified "2023-09-30" @default.
- W2553741326 title "Gene Editing of CCR5 in Hematopoietic Stem Cells in a Nonhuman Primate Model of HIV/AIDS" @default.
- W2553741326 doi "https://doi.org/10.1182/blood.v124.21.4802.4802" @default.
- W2553741326 hasPublicationYear "2014" @default.
- W2553741326 type Work @default.
- W2553741326 sameAs 2553741326 @default.
- W2553741326 citedByCount "1" @default.
- W2553741326 countsByYear W25537413262016 @default.
- W2553741326 crossrefType "journal-article" @default.
- W2553741326 hasAuthorship W2553741326A5001976406 @default.
- W2553741326 hasAuthorship W2553741326A5009781116 @default.
- W2553741326 hasAuthorship W2553741326A5032980660 @default.
- W2553741326 hasAuthorship W2553741326A5039265791 @default.
- W2553741326 hasAuthorship W2553741326A5055711908 @default.
- W2553741326 hasAuthorship W2553741326A5060993908 @default.
- W2553741326 hasAuthorship W2553741326A5073932029 @default.
- W2553741326 hasConcept C104317684 @default.
- W2553741326 hasConcept C109159458 @default.
- W2553741326 hasConcept C111599444 @default.
- W2553741326 hasConcept C126322002 @default.
- W2553741326 hasConcept C159047783 @default.
- W2553741326 hasConcept C203014093 @default.
- W2553741326 hasConcept C207001950 @default.
- W2553741326 hasConcept C2522874641 @default.
- W2553741326 hasConcept C26291073 @default.
- W2553741326 hasConcept C2776185481 @default.
- W2553741326 hasConcept C2777408962 @default.
- W2553741326 hasConcept C2777995582 @default.
- W2553741326 hasConcept C2778086970 @default.
- W2553741326 hasConcept C28328180 @default.
- W2553741326 hasConcept C2911091166 @default.
- W2553741326 hasConcept C502942594 @default.
- W2553741326 hasConcept C54355233 @default.
- W2553741326 hasConcept C71924100 @default.
- W2553741326 hasConcept C86803240 @default.
- W2553741326 hasConcept C95444343 @default.
- W2553741326 hasConceptScore W2553741326C104317684 @default.
- W2553741326 hasConceptScore W2553741326C109159458 @default.
- W2553741326 hasConceptScore W2553741326C111599444 @default.
- W2553741326 hasConceptScore W2553741326C126322002 @default.
- W2553741326 hasConceptScore W2553741326C159047783 @default.
- W2553741326 hasConceptScore W2553741326C203014093 @default.
- W2553741326 hasConceptScore W2553741326C207001950 @default.
- W2553741326 hasConceptScore W2553741326C2522874641 @default.
- W2553741326 hasConceptScore W2553741326C26291073 @default.
- W2553741326 hasConceptScore W2553741326C2776185481 @default.
- W2553741326 hasConceptScore W2553741326C2777408962 @default.
- W2553741326 hasConceptScore W2553741326C2777995582 @default.
- W2553741326 hasConceptScore W2553741326C2778086970 @default.
- W2553741326 hasConceptScore W2553741326C28328180 @default.
- W2553741326 hasConceptScore W2553741326C2911091166 @default.
- W2553741326 hasConceptScore W2553741326C502942594 @default.
- W2553741326 hasConceptScore W2553741326C54355233 @default.
- W2553741326 hasConceptScore W2553741326C71924100 @default.
- W2553741326 hasConceptScore W2553741326C86803240 @default.
- W2553741326 hasConceptScore W2553741326C95444343 @default.
- W2553741326 hasIssue "21" @default.
- W2553741326 hasLocation W25537413261 @default.
- W2553741326 hasOpenAccess W2553741326 @default.
- W2553741326 hasPrimaryLocation W25537413261 @default.
- W2553741326 hasRelatedWork W1988758419 @default.
- W2553741326 hasRelatedWork W2062256187 @default.
- W2553741326 hasRelatedWork W2134662573 @default.
- W2553741326 hasRelatedWork W2367956145 @default.
- W2553741326 hasRelatedWork W2381639528 @default.
- W2553741326 hasRelatedWork W2386230525 @default.
- W2553741326 hasRelatedWork W2414647507 @default.
- W2553741326 hasRelatedWork W2473806260 @default.
- W2553741326 hasRelatedWork W2766749761 @default.
- W2553741326 hasRelatedWork W3198127390 @default.
- W2553741326 hasVolume "124" @default.
- W2553741326 isParatext "false" @default.
- W2553741326 isRetracted "false" @default.
- W2553741326 magId "2553741326" @default.
- W2553741326 workType "article" @default.