Human Immunodeficiency Virus (HIV) is one of the world’s most virulent diseases, affecting approximately 36.1 million people worldwide. The resultant effect of HIV infection is the gradual destruction of the body’s immune system, through infection of crucial helper T-cells. The ultimate objective of medical research is to permanently render these T-cells immune to HIV infection. One emerging scientific field that may hold the key to finding a cure for HIV infection is gene therapy. Gene therapy for HIV is an approach in which genetically engineered genes, capable of expressing proteins lethal to the HIV virion, are transduced into the host cells’ genome.
Hematopoietic stem cells (HSCs) are a desirable target for gene therapy because they offer a permanent source of self-renewing cells capable of differentiating into multiple lineages, including T-cells. Viral vectors, typically retroviruses of oncovirus origin, are used to transduce these cells. However, transduction of HSCs with retroviral vectors poses several technical challenges.
The low level of amphotropic retroviral receptors on the surface of HSCs and the highly quiescent nature of these cells, limit the efficiency of transduction by retrovirus vectors. Improving vector design to increase the transduction efficiency may result in a more therapeutic effect in clinical applications. In addition, developing new cell growth techniques for HSCs will have a significant impact on gene therapy techniques in future years. From a safety aspect, there are concerns that the random integration of the retroviral genome will have a cancerous or lethal effect on the transduced cells. Future research will seek screening and selection methods that will ensure only cells with suitable insertion are used in gene therapy procedures.
The resolution of these technically challenging issues will result in a more successful clinical application of gene therapy for HIV treatment.