Potential Applications and Research Exploration of CRISPRi in the Treatment of Autoimmune Diseases

Shaopu Huang

doi:10.54097/4ahgws64

Authors

Shaopu Huang

DOI:

https://doi.org/10.54097/4ahgws64

Keywords:

CRISPR interference; autoimmune diseases; multiplex gene silencing; immunotherapy.

Abstract

Autoimmune diseases (AIDs) are chronic disorders driven by the breakdown of immune tolerance, where genetic susceptibility and environmental triggers converge to promote aberrant T and B cell activation, inflammatory cytokine release, and progressive tissue damage. Current therapeutic strategies, including corticosteroids, immunosuppressants, and biologics, can alleviate symptoms but remain limited by adverse effects, incomplete remission, and variable patient responses. CRISPR interference (CRISPRi), a novel gene regulation platform based on catalytically inactive Cas9 and guide RNAs, achieves precise, reversible suppression of target genes without inducing DNA double-strand breaks, thereby offering improved safety and controllability over conventional genome editing. Recent studies demonstrate that CRISPRi can effectively silence multiple inflammatory mediators and immune checkpoint molecules, enabling immune microenvironment remodeling and providing a feasible strategy for complex autoimmune conditions. Advances in multiplex CRISPRi, including the design of multi-sgRNA constructs and delivery via viral or non-viral systems, expand its capacity to simultaneously repress synergistic cytokine networks. Despite ongoing challenges in delivery efficiency, off-target risk, and long-term safety, CRISPRi holds considerable promise for network-level therapeutic intervention. This review aims to summarize the principles, technological progress, and potential applications of CRISPRi in autoimmune diseases.

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