CRISPR engineering may make less immunogenic and more useful for regenerative and cancer immunotherapy.
Evidence
This review summarizes recent MSC engineering strategies, including β2-microglobulin knockout, IL-10 or TSG-6 augmentation, TLR4/NF-κB disruption, and antimicrobial or tumor-microenvironment applications.
Caveat
The evidence is synthesized rather than trial-proven, and the abstract highlights off-target editing and delivery optimization as unresolved barriers.
Simplified
(MSCs) have introduced as a cornerstone of regenerative medicine, owing to their immunomodulatory properties and therapeutic potential in autoimmune and inflammatory disorders. Although, their clinical application is often restricted due to immune rejection and heterogeneity in immunoregulatory responses. The advent of Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 () technology has revolutionized MSC engineering, enabling precise genetic modifications to enhance their immunological efficacy. This review explores how CRISPR-mediated editing of MSCs can mitigate immunogenicity, amplify anti-inflammatory functions, and repurpose MSCs for targeted immunotherapy. Key strategies include knockout of β2-microglobulin to evade T-cell recognition, augmentation of anti-inflammatory mediators like interleukin (IL)-10 and TNF-alpha stimulated gene/protein 6 (TSG-6), and disruption of pro-inflammatory pathways such as toll-like receptor 4 (TLR4)/NF-κB. In addition, CRISPR-engineered MSCs demonstrate promise in reshaping tumor microenvironments and combating bacterial infections through enhanced innate immunity. Despite challenges including off-target effects and delivery optimization, CRISPR-tailored MSCs represent a transformative approach to overcoming immunological barriers, paving the way for universal, off-the-shelf therapies in rheumatoid arthritis, cancer, and beyond.
Key numbers
37.3% to 80.2%
Increase in Editing Efficiency
Editing efficiency of β2M knockout in via ribonucleoprotein delivery.
↓ TNF-α, IL-1β, IL-6, MCP-1
Reduction in Pro-inflammatory Cytokines
Cytokine levels following IL-10 overexpression in .
Full Text
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