Protection of Stem Cell-Derived Lymphocytes in a Primate AIDS Gene Therapy Model after In Vivo Selection 英文参考文献.docVIP

下载本文档

7
0
约6.2万字
约 10页
2017-05-13 发布于上海
举报
版权申诉

Protection of Stem Cell-Derived Lymphocytes in a Primate AIDS Gene Therapy Model after In Vivo Selection 英文参考文献.doc

1、本文档共10页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

Protection of Stem Cell-Derived Lymphocytes in a Primate AIDS Gene Therapy Model after In Vivo Selection 英文参考文献

ProtectionofStemCell-DerivedLymphocytesina PrimateAIDSGeneTherapyModelafterInVivoSelection GrantD.Trobridge1,2,RobertA.Wu1,BrianC.Beard1,SumYingChiu1,NinaM.Mun?oz1,Dorotheevon Laer4,JohnJ.Rossi5,Hans-PeterKiem1,2,3* 1ClinicalResearchDivision,FredHutchinsonCancerResearchCenter,Seattle,Washington,UnitedStatesofAmerica,2DepartmentofMedicine,UniversityofWashington, Seattle,Washington, United States ofAmerica, 3Department ofPathology, University ofWashington, Seattle, Washington, United States ofAmerica, 4Georg-Speyer- Haus,InstituteforBiomedicalResearch,Frankfurt,Germany,5DepartmentofMolecularBiology,BeckmanResearchInstituteofCityofHope,Duarte,California,United StatesofAmerica Abstract Background:ThereiscurrentlynoeffectiveAIDSvaccine,emphasizingtheimportanceofdevelopingalternativetherapies. Recently,apatientwassuccessfullytransplantedwithallogeneic,naturallyresistantCCR5-negative(CCR5D32)cells,setting the stage for transplantation of naturally resistant, or genetically modified stem cells as a viable therapy for AIDS. Hematopoietic stem cell (HSC) gene therapy using vectors that express various anti-HIV transgenes has also been attemptedinclinicaltrials,butinefficientgenetransferinthesestudieshasseverelylimitedthepotentialofthisapproach. Herewe evaluated HSC gene transfer of ananti-HIV vector in the pigtailed macaque (Macaca nemestrina) model,which closelymodelshumantransplantation. MethodsandFindings:WeusedlentiviralvectorsthatinhibitedbothHIV-1andsimianimmunodeficiencyvirus(SIV)/HIV-1 (SHIV)chimeravirusinfection,andalsoexpressedaP140Kmutantmethylguaninemethyltransferase(MGMT)transgeneto select gene-modified cells by adding chemotherapy drugs. Following transplantation and MGMT-mediated selection we demonstratedtransgeneexpressioninover7%ofstem-cellderivedlymphocytes.Thehighmarkinglevelsallowedusto demonstrateprotectionfromSHIVinlymphocytesderivedfromgene-modifiedmacaquelong-termrepopulatingcellsthat expressed an HIV-1 fusion inhibitor. We observed a statistically s