Lentiviral transduction and transplantation of hematopoietic stem cells (HSC) can be utilized to modify the phenotype of megakaryocytes and platelets. As the genetic modification in HSC i
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In this study, the scientists introduced promoters of megakaryocyte/platelet-specific genes, namely human glycoprotein 6 (hGP6) and hGP9, into third generation lentiviral vectors and analyzed their functionality in-vitro and in-vivo in bone marrow transplantation assays. They demonstrate that expression from the mPf4 vector in MKs and platelets was the strongest similar to the viral SFFV promoter, however, also exhibit considerable off-target expression in hematopoietic stem and progenitor cells (HSPC). In contrast, the newly generated hGP6 vector was highly specific to megakaryocytes and platelets. The specificity was also retained when reducing the promoter size to 350 bp, making it a valuable new tool for lentiviral expression in MK/platelets.