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Dextran Enhances the Lentiviral Transduction Efficiency of Murine and Human Primary NK Cells. J Vis Exp 2018 Jan 15(131)

Date

01/25/2018

Pubmed ID

29364266

Pubmed Central ID

PMC5908645

DOI

10.3791/55063

Scopus ID

2-s2.0-85041082468 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

The efficient transduction of specific genes into natural killer (NK) cells has been a major challenge. Successful transductions are critical to defining the role of the gene of interest in the development, differentiation, and function of NK cells. Recent advances related to chimeric antigen receptors (CARs) in cancer immunotherapy accentuate the need for an efficient method to deliver exogenous genes to effector lymphocytes. The efficiencies of lentiviral-mediated gene transductions into primary human or mouse NK cells remain significantly low, which is a major limiting factor. Recent advances using cationic polymers, such as polybrene, show an improved gene transduction efficiency in T cells. However, these products failed to improve the transduction efficiencies of NK cells. This work shows that dextran, a branched glucan polysaccharide, significantly improves the transduction efficiency of human and mouse primary NK cells. This highly reproducible transduction methodology provides a competent tool for transducing human primary NK cells, which can vastly improve clinical gene delivery applications and thus NK cell-based cancer immunotherapy.

Author List

Nanbakhsh A, Best B, Riese M, Rao S, Wang L, Medin J, Thakar MS, Malarkannan S

Authors

Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of Wisconsin
Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of Wisconsin
Sridhar Rao MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Dextrans
Genetic Therapy
Humans
Killer Cells, Natural
Lentivirus
Mice