Engineered MSC-exosomes as CRISPR-Cas9 delivery vectors for precision immunotherapy

Mesenchymal stem cell-derived exosomes (MSC-Exos) combined with CRISPR-Cas9 hold substantial therapeutic potential for immune-mediated diseases, although significant technical obstacles remain. This review presents a comprehensive analysis of strategies for engineering MSC-Exos as delivery vehicles for CRISPR-Cas9, with emphasis on cargo-loading methodologies and surface modifications that enable targeting specific immune cell populations. We examine the mechanistic basis for the therapeutic effects of these engineered platforms and critically assess the challenges impeding clinical translation, including manufacturing scalability, safety concerns, and regulatory considerations. Key areas of focus for this Research Topic-vehicle engineering, cargo packaging efficiency, biological barriers, and in vivo safety-are systematically addressed. Finally, we discuss emerging directions, including next-generation gene editors and stimulus-responsive biomaterials. This review provides a balanced framework for advancing MSC-Exos-based nanoplatforms toward precision gene therapies for immune disorders.