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

Ngom M, Imren S, Maetzig T, Adair JE, Knapp DJHF, Chagraoui J, Fares I, Bordeleau ME, Sauvageau G, Leboulch P, Eaves C, Humphries RK

Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver BC V5Z 1L3, Canada.

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.

Mol Ther Methods Clin Dev 2018;10:156-164.

Pubmed ID: 30101153

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