UM171 Enhances Lentiviral Gene Transfer and Recovery of Primitive Human Hematopoietic Cells

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Enhanced gene transfer efficiencies and higher yields of transplantable transduced human hematopoietic stem cells are continuing goals for improving clinical protocols that use stemcell-based gene therapies. Here, we examined the effect of the HSC agonist UM171 on these endpoints in both in vitro and in vivo systems. Using a 22-hr transduction protocol, we found that UM171 significantly enhances both the lentivirus-mediated transduction and yield of CD34+ and CD34+CD45RA- hematopoietic cells from human cord blood to give a 6-fold overall higher recovery of transduced hematopoietic stem cells, including cells with long-term lympho-myeloid repopulating activity in immunodeficient mice. The ability of UM171 to enhance gene transfer to primitive cord blood hematopoietic cells extended to multiple lentiviral pseudotypes, gamma retroviruses, and non-integrating lentiviruses and to adult bone marrow cells. UM171, thus, provides an interesting reagent for improving the ex vivo production of gene-modified cells and for reducing requirements of virus for a broad range of applications.




Ngom, M., Imren, S., Maetzig, T., Adair, J. E., Knapp, D. J. H. F., Chagraoui, J., … Humphries, R. K. (2018). UM171 Enhances Lentiviral Gene Transfer and Recovery of Primitive Human Hematopoietic Cells. Molecular Therapy - Methods and Clinical Development, 10, 156–164.

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