CRISPR-Cas9 Technology for Epigenome Editing in Precision Medicine

CRISPR–Cas9, originally derived from a bacterial adaptive immune system, has rapidly evolved into a transformative platform for genome and epigenome engineering with broad applications in biology and precision medicine. Guided by single-guide RNAs, the Cas9 nuclease introduces targeted DNA modifications through cellular repair pathways. Meanwhile, engineered variants, such as high-fidelity nucleases, nickases, and nuclease-deficient dCas9, extend their functionality to precise gene regulation, epigenetic modulation, RNA editing, and live-cell genomic imaging. dCas9-based effectors enable locus-specific control of transcription by directing DNA methylation, histone modifications, or chromatin remodelling, offering reversible and non-permanent alternatives to conventional epigenetic drugs. In vivo models, including somatically engineered mouse models and xenografts, enable physiologically relevant studies of tumorigenesis and therapeutic response, while base and prime editors offer safer, DNA break–free approaches for the precision correction of pathogenic variants. Clinically, CRISPR is driving innovation in adoptive immunotherapies, regenerative medicine, and targeted delivery systems, with nanoparticle- and ligand-modified carriers improving tissue-specific targeting and reducing systemic toxicity. Despite these advances, major challenges remain, including off-target activity, inefficient and tissue-restricted delivery, instability of epigenetic edits, and ethical concerns surrounding germline modification and long-term safety. Ongoing innovations in CRISPR engineering, delivery technologies, and regulatory oversight are addressing these barriers. Collectively, CRISPR-based platforms represent a cornerstone of next-generation personalised therapeutics, offering programmable, scalable, and clinically relevant strategies to understand and treat human disease.