Gene therapy (GT) has emerged as a promising treatment option for disorders in the hematopoietic system, particularly primary immunodeficiencies (PID). Hematopoietic stem cells (HSCs) have gained attention due to their ability to support long-term hematopoiesis. In this study, we present a summary of research evaluating the most effective method of gene editing in HSCs for translational medicine. We conducted a systematic literature search in various databases, including Cochrane, LILACs, SciELO, and PubMed (MEDLINE), covering the period from January 1989 to June 10, 2023. The aim of this study was to identify articles that assessed the efficiency of gene editing in HSCs and clinical trials focusing on PID. Our research protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42022349850). Of the 470 studies identified in our search, 77 met the inclusion criteria. Among these, 61 studies were included in strategy 1 (gene therapy using HSC [GT-HSC]) of the systematic review (SR). We performed a meta-analysis on 17 of these studies. In addition, 16 studies were categorized under strategy 2 (clinical trials for PID). While clinical trials have demonstrated the potential benefits of GT-HSC, the safety and efficacy of gene editing still pose significant challenges. Various viral and nonviral approaches for gene delivery have been explored in basic and clinical research, with viral vectors being the most commonly used method in HSC therapeutics. Although promising, recent technologies such as CRISPR/Cas are not yet ready for efficient long-term restoration of the immune system as a whole.
Keywords: gene therapy; gene transfer; hematopoietic stem cell; primary immunodeficiency.