Topic: Advances in Gene Therapy for Severe Combined Immunodeficiency (SCID)

Severe Combined Immunodeficiency (SCID) is a group of rare, life-threatening genetic disorders characterized by the absence of functional T cells and, in some cases, B cells and natural killer (NK) cells. This profound immunodeficiency leaves affected infants highly susceptible to severe infections, often leading to death within the first year of life if untreated. Traditional treatments, such as hematopoietic stem cell transplantation (HSCT), have been the cornerstone of SCID management, but they come with significant challenges, including donor availability, graft-versus-host disease (GVHD), and incomplete immune reconstitution.

In recent years, gene therapy has emerged as a promising alternative, offering the potential for a curative approach by directly correcting the underlying genetic defects in patients' own hematopoietic stem cells. Advances in viral vector technology, gene editing tools, and our understanding of the molecular basis of SCID have paved the way for successful clinical trials, demonstrating both immunological reconstitution and long-term clinical benefits in patients with various forms of SCID.

This Special Issue of Journal of Translational Genetics and Genomics (JTGG) invites original research articles, reviews, and perspective pieces that explore the immunological and clinical outcomes of gene therapy in SCID patients. We aim to highlight the latest advancements, challenges, and future directions in this rapidly evolving field. Topics of interest include, but are not limited to:
● Mechanisms of immune reconstitution following gene therapy: Insights into T cell, B cell, and NK cell recovery and functionality
● Long-term clinical outcomes: Survival rates, quality of life, and reduction in infection-related morbidity.
● Comparative efficacy of gene therapy versus HSCT: Benefits, limitations, and patient-specific factors influencing outcomes.
● Safety and adverse effects: Risks of insertional mutagenesis, immune dysregulation, and other potential complications.
● Novel gene-editing technologies: Applications of CRISPR/Cas9, base editing, and prime editing in SCID gene therapy.
● Patient-specific factors influencing gene therapy success: Age at treatment, genetic subtype, and pre-existing conditions.
● Epigenetic and transcriptional regulation in gene-corrected cells: Impact on long-term immune function and stability.
● Emerging strategies to enhance gene therapy efficacy: Optimizing vector design, conditioning regimens, and post-therapy monitoring.
● Ethical and regulatory considerations: Balancing innovation with patient safety in the context of gene therapy for SCID.

We welcome contributions from researchers, clinicians, and translational scientists that provide novel mechanistic insights, clinical data, or perspectives on the future of gene therapy for SCID. By bringing together cutting-edge research and clinical experiences, this Special Issue aims to advance our understanding of the immunological and clinical outcomes of gene therapy, fostering the development of safer, more effective treatments for SCID patients. We look forward to your submissions and to advancing this critical area of research together.

SCID, gene therapy, immune reconstitution, stem cell transplantation, gene editing

30 Sep 2025