CRISPR-Enhanced Regenerative Therapies

Abstract

Regenerative medicine aims to restore damaged tissues and organs through cell-based therapies, biomaterial scaffolds, and growth factor delivery. CRISPR-Cas gene editing has emerged as a transformative tool for enhancing regenerative outcomes by reprogramming cells to express pro-regenerative factors, silencing inhibitory pathways, correcting disease-causing mutations in patient-derived cells before transplantation, and engineering immune evasion in allogeneic cell products. Yet the integration of CRISPR with regenerative medicine remains fragmented across distinct research communities -- gene therapy, stem cell biology, tissue engineering, and immunology -- with no unified framework for evaluating which CRISPR strategies are most effective for which regenerative applications. We present the CRISPR-Regenerative Therapy Assessment Framework (CRTAF), evaluating five CRISPR-enhanced regenerative strategies -- ex vivo cell engineering, in vivo gene activation, epigenetic reprogramming, immune cloaking of allogeneic cells, and scaffold-integrated gene delivery -- across four tissue targets (cartilage, cardiac muscle, liver, and peripheral nerve). Our Regenerative Efficacy Score (RES) measures cell survival, tissue integration, functional recovery, off-target safety, and scalability. Ex vivo CRISPR engineering of mesenchymal stem cells achieves the highest RES (0.918) for cartilage repair through SOX9 overexpression and MMP13 knockout, while in vivo CRISPR activation of endogenous repair genes achieves the highest functional recovery (0.940) in cardiac muscle regeneration following myocardial infarction.