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Hum Gene Ther Methods. 2018 Apr;29(2):104-113. doi: 10.1089/hgtb.2017.085.

Improving Lentiviral Transduction of CD34+ Hematopoietic Stem and Progenitor Cells.

Author information

1
1 Heinrich Pette Institute - Leibniz Institute for Experimental Virology , Hamburg, Germany.
2
2 German Center for Infection Research (DZIF) , Partner Site Hamburg, Germany.
3
3 SIRION Biotech GmbH, Planegg-Martinsried , Germany.
4
4 Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf , Hamburg, Germany .

Abstract

The delivery of therapeutic genes for treatment of inherited or infectious diseases frequently requires lentiviral transduction of CD34+ hematopoietic stem and progenitor cells (HSC). Optimized transduction protocols with a therapeutic goal aim to maximize the number of transduction-positive cells while limiting the vector copy number that reach each individual cell. Importantly, the transduced HSC should maintain their "stem-like" properties. Here, we analyzed LentiBOOST™ reagent, a membrane-sealing poloxamer, with respect to enhancing lentiviral transduction of CD34+ peripheral blood stem cells. We demonstrate that inclusion of LentiBOOST™ in a standard HSC transduction protocol yields high transduction efficiencies while preserving the ability of the transduced HSC to differentiate into various hematopoietic lineages. Thus, LentiBOOST™ reagent can significantly improve lentiviral CD34+ HSC transduction protocols with the potential to improve production of gene-modified cell products.

KEYWORDS:

CD34+ HSC; PBSC; gene therapy; lentiviral vector; transduction

PMID:
29631437
DOI:
10.1089/hgtb.2017.085
[Indexed for MEDLINE]

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