In vivo selection of genetically modified erythroid cells using a jak2-based cell growth switch

Molecular Therapy : the Journal of the American Society of Gene Therapy
Shengming ZhaoC Anthony Blau

Abstract

Cell-based therapies have potential widespread applications in clinical medicine, and methods for controlling the fate of transplanted cells are needed. We have previously described a means for directing the growth of genetically modified cells in vivo using a derivative of the thrombopoietin receptor, mpl, that is reversibly activated by a drug called a chemical inducer of dimerization (CID). Since Jak2 participates in signaling from a number of different cytokine receptors (including mpl), we tested whether direct activation of the JH1 domain of Jak2 would broaden the repertoire of hematopoietic lineages responsive to the CID. While the engineered Jak2 induced a significant rise in genetically modified red cells, as we have observed previously with mpl, it lacked mpl's ability to expand genetically modified platelets and failed to expand genetically modified granulocytes, B cells, or T cells. These findings identify a signaling molecule other than mpl that can function as a cell growth switch in vivo and demonstrate that signaling molecules used for in vivo selection need not be confined to receptors. The erythroid-restricted growth response suggests that CID-activated Jak2 may be well suited to gene therapy applications in s...Continue Reading

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Citations

Aug 12, 2006·Blood·Michael A WeinreichC Anthony Blau
Feb 18, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kiyoshi OkazukaC Anthony Blau
Mar 15, 2012·Expert Opinion on Biological Therapy·Roberto Gambari
Nov 21, 2007·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Anton NeschadimJeffrey A Medin
Mar 22, 2008·Gene Therapy·C P Miller, C A Blau
Mar 30, 2006·The Journal of Gene Medicine·Wilfried Weber, Martin Fussenegger
Jul 20, 2019·Biomarker Research·Boguslaw A KwiatkowskiRobert E Richard
Aug 4, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Christopher SiatskasJeffrey A Medin
Jun 21, 2013·Expert Review of Hematology·Laura BredaRoberto Gambari
Apr 1, 2010·Chemical Reviews·Adrian FeganCarston R Wagner
Jun 15, 2006·Chemical Reviews·Daniel P Walsh, Young-Tae Chang

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