Abstract
Despite the enormous success of combined anti-retroviral therapy, HIV infection is still a lifelong disease and continues to spread rapidly worldwide. There is a pressing need to develop a treatment that will cure HIV infection. Recent progress in stem cell manipulation and advancements in humanized mouse models have allowed rapid developments of gene therapy for HIV treatment. In this review, we will discuss two aspects of HIV gene therapy using human hematopoietic stem cells. The first is to generate immune systems resistant to HIV infection while the second strategy involves enhancing anti-HIV immunity to eliminate HIV infected cells.
Highlights
The success of antiretroviral therapy in HIV infection has changed the landscape of HIV disease
Subsequent study using the humanized mouse model showed that CCR5 gene was disrupted in 17% of human CD34+ hematopoietic cells by ZFN via nucleofection and the modified cells were successfully engrafted in NOD/SCID/IL2rγnull (NSG) mice
Efforts are directed at combining both of these approaches and attempting to protect engineered HIV-specific immune cells from HIV infection
Summary
The success of antiretroviral therapy in HIV infection has changed the landscape of HIV disease. Active antiretroviral therapy (HARRT), if initiated before advanced disease stages and if properly adhered to, can potently reduce the plasma HIV viral load to low or undetectable levels in most patients. This has changed what used to be a universally fatal disease to a potentially chronic disease. Despite this success, antiretroviral therapy is not completely effective; chronic inflammation and immune dysfunction often persist and emerging evidence shows that there is cryptic viral replication in dispersed lymphoid organs during treatment [1]. These two strategies represent the cutting edge of current gene therapy approached towards HIV infection and, alone or in combination with other strategies, have the potential to eradicate HIV
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