The future of pediatric gene therapy: CRISPR-Cas9, AI, and personalized medicine.

The future of pediatric gene therapy is being fundamentally reshaped by the convergence of CRISPR-Cas9 genome editing, artificial intelligence (AI), and personalized medicine, providing unprecedented opportunities for the treatment of rare and previously intractable genetic disorders in children. CRISPR-Cas9 enables precise and potentially curative correction of pathogenic mutations underlying conditions, such as sickle cell disease, cystic fibrosis, and Duchenne muscular dystrophy, with particularly notable progress in hematological disorders. AI-driven tools, like DeepCRISPR and CRISPR-GPT are emerging as valuable assets for streamlining experimental design, prioritizing candidate edits, and accelerating preclinical-to-clinical translation. In parallel, advances in delivery systems, including adeno-associated viral (AAV) vectors and non-viral platforms such as lipid nanoparticles (LNPs), are expanding the feasibility of both ex vivo and in vivo pediatric applications. The synergistic integration of CRISPR-Cas9, AI, and personalized medicine enables more precise, patient-specific therapeutic strategies that better account for the developmental, physiological, and genetic heterogeneity of pediatric populations. Addressing these challenges will require interdisciplinary collaboration across genome engineering, AI science, clinical pediatrics, bioethics, and regulatory policy. The establishment of standardized regulatory frameworks, accompanied by robust and transparent AI integration, will be essential to ensure safe, equitable, and scalable translation. IMPACT: The future of pediatric gene therapy is being reshaped by the integration of CRISPR-Cas9, AI, and personalized medicine. We review recent clinical trials, including ex vivo CRISPR-Cas9 applications for hemoglobinopathies. This article emphasizes interdisciplinary collaboration to overcome these barriers. Pediatric gene therapy holds transformative potential to provide curative solutions for children.