A scoping review of gene editing in clinical trials: identifying aspects of trial design to accelerate clinical adoption.

BACKGROUND

Initial clinical trials of gene editing have recently emerged and generated significant interest in this promising therapy. A scoping review is needed to understand aspects of study design that may accelerate further clinical translation.

METHODS

A systematic search of published clinical trials was conducted to May 22, 2025.

RESULTS

Twenty-nine published trials were identified for analysis (420 patients; median ages 6 months to 90 years). The most common gene editing technology used was CRISPR-Cas9 (23 studies, 79%). Hematopoietic cells were targeted most frequently, and leukemias and lymphomas were the most common clinical indications (8 studies; 27.5%), followed by hemoglobin disorders (6; 20.6%), solid tumors (6; 20.6%), rare genetic diseases (5; 17.2%), and others (4; 13.8%). All trials were early-phase (Phase I/II) with only 1 controlled study (29 patients). Six studies used in vivo approaches while all others performed gene editing ex vivo. Gene transfection was by electroporation (9 studies; 31.0%), viral-mediated transfection (6; 20.7%), or by lipid nanoparticles (3; 10.3%). Commonly reported outcomes included early safety and adverse events, mortality, persistence of edited cells, clinical and functional responses. Studies of leukemia/lymphoma reported rates of complete remission in 15-92% while we identified important and sustained increases in mean hemoglobin levels in studies of hemoglobin disorders. Edited cells were detected in most studies at 3 and 6 months but later timepoints were reported less frequently. While early serious adverse events were infrequently observed, reporting of longer-term outcomes was lacking.

CONCLUSION

Gene editing appears feasible and generally safe in humans although important safety outcomes such as long-term oncogenic surveillance outcomes remain to be addressed. A broad range of conditions have been treated, and most often leverages the CRISPR-Cas9 technology with transfection by electroporation. The persistence of edited cells remains ill-defined and longer-term safety outcomes are needed. Studies optimizing CART therapy for leukemia/lymphoma and treatment of hemoglobin disorders appear poised for significant clinical adoption.