Gene Therapy Approaches to Functional Cure and Protection of Hematopoietic Potential in HIV Infection

Abstract

Although current antiretroviral drug therapy can suppress the replication of human immunodeficiency virus (HIV), a lifelong prescription is necessary to avoid viral rebound. The problem of persistent and ineradicable viral reservoirs in HIV-infected people continues to be a global threat. In addition, some HIV-infected patients do not experience sufficient T-cell immune restoration despite being aviremic during treatment. This is likely due to altered hematopoietic potential. To achieve the global eradication of HIV disease, a cure is needed. To this end, tremendous efforts have been made in the field of anti-HIV gene therapy. This review will discuss the concepts of HIV cure and relative viral attenuation and provide an overview of various gene therapy approaches aimed at a complete or functional HIV cure and protection of hematopoietic functions.

Hematopoietic Stem/Progenitor Cells and the Pathogenesis of HIV/AIDS

“…Recent studies indicate HSPCs as an ideal target for anti-HIV gene therapy aimed to protect hosts' hematopoietic potential (Kitchen et al, 2011;Savkovic et al, 2014). For detailed discussions on recent advances in the field, see a recently published review by this author Tsukamoto (2019a).…”

Ready for Repair? Gene Editing Enters the Clinic for the Treatment of Human Disease

“…CCR5 knockdown by short hairpin RNA (shRNA) in HSCs or T cells has been readily tested in preclinical studies and is the subject of a phase I/II clinical trial. 221 Targeting of HIV transcripts by RNAi has also been tested preclinically. 221 Besides mutational esacape mentioned above, RNAi faces the additional challenge of transcriptional upregulation of the target in response to knockdown.…”

“… 221 Targeting of HIV transcripts by RNAi has also been tested preclinically. 221 Besides mutational esacape mentioned above, RNAi faces the additional challenge of transcriptional upregulation of the target in response to knockdown. 222 …”

“…221 Targeting of HIV transcripts by RNAi has also been tested preclinically. 221 Besides mutational esacape mentioned above, RNAi faces the additional challenge of transcriptional upregulation of the target in response to knockdown. 222 Exciting preclinical studies have shown the feasibility for applying gene editing to the engineering of B cells that produce antibodies specific to a number of viruses, including Rous sarcoma virus (RSV), influenza virus, Epstein-Barr virus (EBV), or HIV, all of which are viruses for which there is to date no vaccine available.…”

Novel Approaches for the Delivery of Anti-HIV Drugs—What Is New?

“…The Special Issue starts with an interesting review by Tsukamoto at Kindai University, Japan, on strategies explored for curing HIV infection using a combination of gene therapy and host immunization [20]. In particular, the author emphasizes the possible role of anti-HIV intracellular immunization using gene silencing, among other approaches, in the protection of bone marrow hematopoietic stem/progenitor cells.…”