Exploring the synergy of CRISPR and microphysiological systems
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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.
Plain language summary
CRISPR-Cas9 gene editing technology offers promising potential for treating genetic diseases by correcting mutations. However, its safe application faces challenges due to limitations in testing models. Traditional laboratory methods using immortalized cells or animal studies often fail to accurately reflect human responses. Microphysiological systems (MPS), also known as "organs-on-chips," represent an innovative alternative that can better mimic human tissue structure and function. This review explores how combining CRISPR technology with MPS can enhance both fields: MPS provides more relevant testing platforms for CRISPR therapies, while CRISPR enables creation of disease models in MPS. This synergy could lead to safer, more effective gene therapies and reduce the need for animal testing. By offering more accurate prediction of human responses, this approach addresses current limitations in translating laboratory findings to clinical applications, ultimately benefiting patients with genetic disorders.
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