Monitoring biological effects of somatic cell genome editing.

PubMed ID: 41530266

Author(s): Freedman BS, Bulte JWM, Conklin BR, Judge LM, Dwinell MR, Geurts AM, Sitton MJ, Mahajan V, Kiani S, Gersbach CA, Ebrahimkhani MR, Kelly JJ, Ronald JA, Morizane R, Gupta N, Shakeri-Zadeh A, Vo N, Saha K, Saxena S, Gamm DM, Sinha D, Tarantal AF, Vandsburger M, Matsubara A, Fu H, Tsai SQ; SCGE Dissemination and Coordinating Center Toolkit Team; SCGE Biological Effects Initiative. Monitoring biological effects of somatic cell genome editing. Nat Rev Genet. 2026 Jan 13. doi: 10.1038/s41576-025-00916-0. Online ahead of print. PMID 41530266

Journal: Nature Reviews. Genetics, Jan 2026

CRISPR-based genome editing therapeutics are entering the clinic, offering transformative potential but also presenting potential risks. Preclinical-to-clinical toolkits are needed to assess the safety and efficacy of these new therapies and accelerate progress. Emerging technologies to monitor the biological effects of genome editors cover a range of biological scales, from the direct measurement of editing outcomes in DNA, to human microphysiological systems, and non-invasive in vivo imaging. Measurements of on-target and off-target editing outcomes, including sequences unique to humans, provide essential benchmarks to understand functional responses. Microphysiological systems, including organoids and organs-on-chips, enable phenotypic evaluations of editing strategies in varied organ lineages and disease states. Non-invasive imaging modalities can track the biodistribution and activities of genome editors and edited cells in vivo. Collectively, these technologies provide complementary insights across different scales, from the single nucleotide to the whole organism, bridging preclinical therapeutics development with clinical trials.