Harnessing CRISPR technology for next-generation microphysiological systems

Microphysiological systems (MPSs) bridge traditional cell cultures and animal models, recapitulating human organ functions and disease characteristics. Despite their promise, MPSs face limitations like genetic diversity and disease phenotype replication. Recent advancements have integrated CRISPR/Cas gene editing into MPSs to address these challenges and enhance disease-specific models. This review explores the latest trends in MPS and CRISPR technologies, examining their fundamentals and current state. It details the utilization of CRISPR/Cas within in vitro systems, including traditional cell cultures and MPSs, focusing on mimicking organ structures and functions like the blood-brain barrier, brain, and kidney and optimizing cell culture conditions. Our review highlights applications of CRISPR-applied MPSs in translational science, such as studying disease mechanisms, identifying therapeutic targets, and developing drugs. We also discuss CRISPR-MPS platforms' challenges, limitations, and future perspectives, emphasizing their potential to meet unmet needs in emerging MPS developments.