Translating CRISPR-Cas Systems into musculoskeletal medicine and orthopaedics: a scoping review protocol

BackgroundMusculoskeletal diseases are a leading cause of global disability and healthcare burden, yet traditional orthopaedic procedures often fail to address molecular drivers of degenerative and genetic conditions. CRISPR-Cas Systems, a precise and programmable genome-editing technology, show promise in preclinical musculoskeletal models, ranging from gene knockouts in osteoarthritis to mutation correction in skeletal dysplasia. Despite growing interest, no comprehensive synthesis exists to map how CRISPR-Cas Systems are being applied in orthopaedic research. This scoping review aims to fill that gap. MethodsThis protocol will be registered with the Open Science Framework and follows PRISMA-ScR guidelines and the Arksey & OMalley framework. MEDLINE, Embase, Scopus, Web of Science, and grey literature sources from 2005 onward will be searched. Inclusion criteria encompass original research using CRISPR-Cas Systems in human, animal, or in vitro musculoskeletal models. Two reviewers will independently screen titles, abstracts, and full texts using Covidence software. Data extraction will be standardized and performed in duplicate. Extracted variables include study design, model system, target tissue, gene-editing approach, delivery system, and reported outcomes. Results will be synthesized descriptively and thematically. Expected ResultsWe anticipate mapping the evolution and diversity of CRISPR-Cas Systems applications across musculoskeletal tissues (bone, cartilage, tendon, muscle), highlighting domains such as tissue regeneration, gene correction, and disease modeling. Delivery strategies (viral vectors, nanoparticles) and translational challenges, including off-target effects and delivery barriers, will be summarized. ConclusionsThis will be the first scoping review to systematically characterize the role of CRISPR-Cas Systems in musculoskeletal medicine. Findings will inform researchers, clinicians, and policymakers, helping to guide future translational research and accelerating the integration of gene editing into clinical practice.