GENE-CELL THERAPY OF HIV AND HEMATOLOGICAL MALIGNANCES BASED ON HEMATOPOIETIC STEM CELL TRANSPLANTATION AND SITE-SPECIFIC GENOME EDITING

Abstract

Based on the annual UNAIDS reports the number of HIVinfected patients is continually growing since 1983. Antiretroviral Therapy (ART) allows to prolong life expectancy, but the problem of life quality and overall survival is still remaining. Nowadays, in the era of ART, one of the main cause of mortality in HIV-infected patients is malignancies. Lymphomas play one of the key roles in this group of diseases. The treatment of lymphomas includes combined regiments of chemotherapy with a curative potential. High dose chemotherapy with autologous hematopoietic stem cell transplant (auto-HSCT) is the main path of the treatment for relapsed / refractory lymphomas. In the last few years with a development of the genome editing technology auto-HSCT is becoming one of the most promising methods of HIV treatment. The case of “Berlin patient” when allogeneic HSCT from donor with mutation CCR5-delta32 lead to cure from HIV and proof of concept the efficacy of the gene therapy for HIV based on HSCT. Hematopoietic stem cell transplantation with edited autologous HSC (CCR5 knockout by site-specific genome editing tools with engineering nucleases) is a comprehensive treatment for this cohort of patients. On one hand, high dose chemotherapy with auto-HSCT cures the malignancy; on the other hand auto-HSCT works as a delivery method for the edited cells and creates an environment for the HIV eradication. This review is dedicated to HIV and oncology, methods of treatment of hematological malignancies and HIV-infection using genome editing technology based on HSCT.

Keywords

• hiv
• gene cell therapy
• ccr5
• genome editing
• zfn
• talen
• crispr/cas9