Emerging gene therapy approaches for the treatment of severe combined immunodeficiency (SCID): a comprehensive review

Abstract

Background. Severe Combined Immunodeficiency (SCID) is a life-threatening condition resulting from various genetic mutations that impair immune cell development. Traditional treatment via hematopoietic stem cell transplantation (HSCT) has limitations, prompting exploration into gene therapy as a promising alternative. Objectives. This review aims to evaluate emerging gene therapy approaches for SCID, emphasizing the use of lentiviral vectors and CRISPR/Cas9 technology, and to assess their efficacy and safety in comparison to traditional HSCT. Materials and Methods. A comprehensive literature search was conducted using PubMed and Google Scholar to identify peer-reviewed articles, clinical trials, and observational studies on gene therapy for SCID published in the last 10 years. Studies were included based on their relevance to gene therapy interventions, and outcomes related to efficacy and safety were analyzed. Discussions. Gene therapy has shown significant promise in SCID treatment, particularly through the use of lentiviral vectors and CRISPR/Cas9 for precise genetic correction. Clinical trials demonstrate improved immunological reconstitution and patient outcomes, with reduced side effects compared to HSCT. However, challenges such as optimizing protocols, ensuring long-term safety, and equitable access to treatments remain. Ongoing research and trials continue to advance our understanding, offering hope for more effective, personalized SCID therapies in the future.