Exploring the synergy of CRISPR and microphysiological systems.

Abstract

Since its discovery as an innate bacterial immune system, the Clustered regularly interspaced short palindromic repeats (CRISPR) associated nuclease 9 (CRISPR-Cas9) system has quickly landed on mammalian genomes to become the first-in-class editing technique. CRISPR-Cas9 offered an invaluable approach to correct pathogenic mutations, thus becoming a promising cure for diseases with highly unmet medical needs. To date, several attempts with different degrees of success were done to understand, categorize and predict the outcome of genetic manipulation. The lack of an appropriate and translatable model to test CRISPR/Cas9 effects, both wanted and unwanted, has therefore limited its applications to advance gene therapies. Herein we describe the potential of microphysiological systems (MPS) as an alternative to the classical surrogates used in CRISPR safety studies, such as immortalized cell lines or small mammals (e.g. rodents), to facilitate the progress of new CRISPR medicines to the clinics.