Abstract
Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV) infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC). Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a potentially safer integration profile. This review focuses on novel anti-HIV transgenes and the potential of foamy virus vectors for HSC gene therapy of HIV.
Highlights
The latest statistics show that nearly 36.9 million people are living with Human ImmunodeficiencyVirus (HIV) and should be receiving treatment against Human Immunodeficiency Virus (HIV) infection [1]
This review focuses on the potency of anti-HIV transgenes and the potential of Foamy viral (FV) vectors for delivering anti-HIV transgenes
At least two studies revealed that anti-rev siRNA expression significantly drops LV viral vector titer up to 2 logs, whereas the same anti-HIV transgene had no significant effect on the titers of FV vectors [23,27]
Summary
Virus (HIV) and should be receiving treatment against HIV infection [1]. Highly active antiretroviral therapy (HAART) is the current standard of care which is a combination of drugs that effectively suppress HIV infection and increase the life expectancy of patients [2,3]. HSC gene therapy has been used to successfully treat monogenic diseases including adenosine deaminase deficient-severe combined immunodeficiency (ADA-SCID), X-linked SCID, X-linked adrenoleukodystrophy and hemophilia B [14] In these HSC gene therapy clinical studies retroviral-based vector systems, gammaretroviral (GRV) or lentiviral (LV) vectors, were used to mediate permanent delivery of the therapeutic transgene [15]. In the HSC gene therapy setting non-integrating vectors have not yet been effective in large animal models or in patients [15] This advantage of retroviral vectors creates a problem. This review focuses on the potency of anti-HIV transgenes and the potential of FV vectors for delivering anti-HIV transgenes
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