Stimuli-responsive CRISPR-based genome editing delivery system for cancer treatment: A review of fundamentals and applications

Cancer remains a leading cause of mortality worldwide. Conventional modalities, namely surgery, radiotherapy, chemotherapy, and immunotherapy, continue to face substantial limitations. The advent of gene therapy, particularly CRISPR-based genome editing, offers new opportunities to overcome these barriers. Nuclease systems such as CRISPR/Cas9 enable precise excision of mutant alleles and targeted insertion of exogenous sequences by harnessing endogenous DNA-repair pathways, achieving durable and accurate genomic modification; derivative tools including CRISPRi, base editing, and prime editing enable diverse forms of gene regulation or precise genome modification through transcriptional repression, base conversion, or related editing mechanisms. To enhance the efficiency, specificity, and spatiotemporal control of CRISPR editing in vivo, sophisticated delivery platforms have been engineered to respond to endogenous tumor-microenvironment cues (e.g., pH, redox potential, hypoxia, ATP, enzymes and microRNAs) or exogenous triggers (e.g., light, ultrasound and magnetic fields). Distinct from material-centric classification schemes, this review organizes these stimuli-responsive systems according to their pathological relevance to the tumor microenvironment (TME), establishing a conceptual framework that links specific TME aberrations with corresponding delivery paradigms. These stimuli-responsive systems represent a major innovation and markedly expand the therapeutic potential of genome editing in oncology. In this review, we summarize the mechanistic basis of CRISPR-based editing, delineate design principles and engineering strategies for stimuli-responsive delivery, and highlight recent advances, outstanding challenges, and future directions toward clinical translation. We aim to provide a concise reference to guide the rational design of gene-editing cancer therapeutics.

Abstract from PubMed (PMID 43009024). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.