| Summary: | The costs and incidence of musculoskeletal injuries are rapidly increasing due to rising population age, higher prevalence of risk factors, and lack of effective long-term treatments. Regenerative medicine addresses the demand for treatments using biological cues to stimulate progenitor cells to create engineered tissues for engraftment at injury sites. However, traditional regenerative therapies are challenged by broad phenotypic changes and high risks of undesirable and systematic side-effects. In comparison to the delivery of recombinant growth factors and gene delivery approaches, clustered regularly interspaced short palindromic repeats (CRISPR) gene editing facilitates direct, specific, and tunable modification of gene expression to enable fine control over cell fate and behavior. This technology has proven to be a potent tool for the treatment of genetic diseases that impact the musculoskeletal system, such as Duchenne muscular dystrophy. However, its potential extends beyond the treatment of genetic disorders, as it also holds promise in augmenting tissue repair in patients suffering from traumatic injuries and inflammatory conditions. This review delves into the recent progress and future prospects of CRISPR-based strategies in musculoskeletal tissue engineering. Particular emphasis is placed on describing the different CRISPR modalities, delivery systems and their mechanisms of action, highlighting their potential in enhancing the repair of bone, cartilage, skeletal muscle, tendon, and ligament tissues.
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