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dc.contributor.authorHahn, Katharina
dc.contributor.authorPollmann, Liart
dc.contributor.authorNowak, Juliette
dc.contributor.authorNguyen, Ariane Hai Ha
dc.contributor.authorHaake, Kathrin
dc.contributor.authorNeehus, Anna-Lena
dc.contributor.authorWaqas, Syed F Hassnain
dc.contributor.authorPessler, Frank
dc.contributor.authorBaumann, Ulrich
dc.contributor.authorHetzel, Miriam
dc.contributor.authorCasanova, Jean-Laurent
dc.contributor.authorSchulz, Ansgar
dc.contributor.authorBustamante, Jacinta
dc.contributor.authorAckermann, Mania
dc.contributor.authorLachmann, Nico
dc.date.accessioned2020-05-12T09:36:15Z
dc.date.available2020-05-12T09:36:15Z
dc.date.issued2020-04-11
dc.date.submitted2020-05-12
dc.identifier.citationMol Ther Methods Clin Dev. 2020 Apr 11;17:785-795. doi: 10.1016/j.omtm.2020.04.002. eCollection 2020 Jun 12.en_US
dc.identifier.issn2329-0501
dc.identifier.pmid32355867
dc.identifier.doi10.1016/j.omtm.2020.04.002
dc.identifier.urihttp://hdl.handle.net/10033/622257
dc.description.abstractAutosomal recessive (AR) complete interferon-γ receptor 1 (IFN-γR1) deficiency, also known as one genetic etiology of Mendelian susceptibility to mycobacterial disease (MSMD), is a life-threatening congenital disease leading to premature death. Affected patients present a pathognomonic predisposition to recurrent and severe infections with environmental mycobacteria or the Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine. Current therapeutic options are limited to antibiotic treatment and hematopoietic stem cell transplantation, however with poor outcome. Given the clinical success of gene therapy, we introduce the first lentiviral-based gene therapy approach to restore expression and function of the human IFN-γR-downstream signaling cascade. In our study, we developed lentiviral vectors constitutively expressing the human IFN-γR1 and demonstrate stable transgene expression without interference with cell viability and proliferation in transduced human hematopoietic cells. Using an IFN-γR1-deficient HeLa cell model, we show stable receptor reconstitution and restored IFN-γR1 signaling without adverse effect on cell functionality. Transduction of both SV40-immortalized and primary fibroblasts derived from IFN-γR1-deficient MSMD patients was able to recover IFN-γR1 expression and restore type II IFN signaling upon stimulation with IFN-γ. In summary, we highlight lentiviral vectors to correct the IFN-γ mediated immunity and present the first gene therapy approach for patients suffering from AR complete IFN-γR1 deficiency.en_US
dc.language.isoenen_US
dc.publisherElsevier(Cell Press)en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectGene Therapyen_US
dc.subjectIFN-γR1 deficiencyen_US
dc.subjectLentiviral Vectorsen_US
dc.subjectMSMDen_US
dc.titleHuman Lentiviral Gene Therapy Restores the Cellular Phenotype of Autosomal Recessive Complete IFN-γR1 Deficiency.en_US
dc.typeArticleen_US
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.en_US
dc.identifier.journalMolecular therapy. Methods & clinical developmenten_US
dc.source.volume17
dc.source.beginpage785
dc.source.endpage795
refterms.dateFOA2020-05-12T09:36:16Z
dc.source.journaltitleMolecular therapy. Methods & clinical development
dc.source.countryUnited States


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