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Cytokine stimulation and the choice of promoter are critical factors for the efficient transduction of mouse T cells with HIV-1 vectors

✍ Scribed by David E. Gilham; Michael Lie-A-Ling; Naomi Taylor; Robert E. Hawkins


Publisher
John Wiley and Sons
Year
2009
Tongue
English
Weight
589 KB
Volume
12
Category
Article
ISSN
1099-498X

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✦ Synopsis


Abstract

Background

HIV‐1 fails to successfully infect mouse T cells as a result of several blocks in the viral replication cycle. We investigated whether this also impacted on the use of HIV‐1 derived lentiviral vectors for stable gene transfer into mouse T cells.

Methods

Freshly isolated primary mouse T cells were immediately mixed with lentiviral vectors encoding an enhanced green fluorescent protein marker gene and transduction frequency was determined after 5 days of culture.

Results

Optimal transduction required both mouse T cell activation and cytokine support. Furthermore, transduction was also dependent upon the promoter chosen, with the rank order of potency being PGK > EF1 > SFFV > CMV. HIV‐1 lentiviral vectors also efficiently transduced cytokine‐stimulated T cells (in the absence of antibody driven T cell activation), albeit with a lower level of transgene expression compared to fully‐activated T cells.

Conclusions

The present study demonstrates that primary mouse T cells can be efficiently transduced with HIV‐1 lentiviral vectors, opening up prospects for their use in mouse models of gene‐modified adoptive cellular therapy. Copyright © 2009 John Wiley & Sons, Ltd.