Conditional Cytotoxic Anti-HIV Gene Therapy for Selectable Cell Modification

Human Gene Therapy
Himanshu Garg, Anjali Joshi

Abstract

Gene therapy remains one of the potential strategies to achieve a cure for HIV infection. One of the major limitations of anti-HIV gene therapy concerns recovering an adequate number of modified cells to generate an HIV-proof immune system. Our study addresses this issue by developing a methodology that can mark conditional vector-transformed cells for selection and subsequently target HIV-infected cells for elimination by treatment with ganciclovir (GCV). We used the herpes simplex virus thymidine kinase (TK) mutant SR39, which is highly potent at killing cells at low GCV concentrations. This gene was cloned into a conditional HIV vector, pNL-GFPRRESA, which expresses the gene of interest as well as green fluorescent protein (GFP) in the presence of HIV Tat protein. We show here that TK-SR39 was more potent that wild-type TK (TK-WT) at eliminating infected cells at lower concentrations of GCV. As the vector expresses GFP in the presence of Tat, transient expression of Tat either by Tat RNA transfection or transduction by a nonintegrating lentiviral (NIL) vector marked the cells with GFP for selection. In cells selected by this strategy, TK-SR39 was more potent at limiting virus replication than TK-WT. Finally, in Jurkat cells ...Continue Reading

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Citations

Jun 5, 2019·Pharmaceutics·Nejat Düzgüneş, Krystyna Konopka
Feb 1, 2021·Virology Journal·Tugba Mehmetoglu-GurbuzAnjali Joshi
Jun 2, 2021·Virology Journal·Sepideh SaebChristian Schwartz

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Methods Mentioned

BETA
transfection
genetic modification
flow cytometry
flow
fluorescence microscopy

Software Mentioned

SigmaPlot
Excel
FlowJo
NIS
Omega
Elements AR
FloJo

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