Abstract
Highly active antiretroviral therapy (HAART) has vastly improved outcomes for patients infected with HIV, yet it is a lifelong regimen that is expensive and has significant side effects. Retroviral gene therapy is a promising alternative treatment for HIV/AIDS; however, inefficient gene delivery to hematopoietic stem cells (HSCs) has so far limited the efficacy of this approach. Foamy virus (FV) vectors are derived from non-pathogenic viruses that are not endemic to the human population. FV vectors have been used to deliver HIV-inhibiting transgenes to human HSCs, and they have several advantages relative to other retroviral vectors. These include an attractive safety profile, broad tropism, a large transgene capacity, and the ability to persist in quiescent cells. In addition, the titers of FV vectors are not reduced by anti-HIV transgenes that affect the production of lentivirus (LV) vectors. Thus FV vectors are very promising for anti-HIV gene therapy. This review covers the advantages of FV vectors and describes their preclinical development for anti-HIV gene therapy.
Highlights
Active antiretroviral therapy (HAART) has vastly improved outcomes for patients infected with HIV, yet it is a lifelong regimen that is expensive and has significant side effects
hematopoietic stem cells (HSCs) carrying anti-HIV transgenes would persist over the lifetime of the patient, continually producing differentiated daughter cells that are protected against HIV infection
CD34 cells transduced with an Foamy virus (FV) vector that incorporated an anti-HIV transgene cassette and
Summary
HIV infection remains a global health crisis. There were an estimated 34 million cases worldwide in. HAART has greatly improved outcomes for individuals living with HIV [2,3]. It efficiently inhibits viral replication and is highly effective at suppressing viral loads. HAART therapy has not been able to target latent proviruses residing in long-lived cellular reservoirs [4]. These reservoirs appear to be stable [5], and they are thought to be the source of the low level viremia that is typically observed over the lifetime of an HIV patient on HAART [4,5]. HAART has served as the cornerstone of anti-HIV therapeutics for nearly two decades, it has limitations that justify the exploration of alternative treatments
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