Precision Delivery of CRISPR/Cas Systems via DNA Nanostructures for Gene Therapy and Intracellular Detection

The CRISPR/Cas system represents a transformative breakthrough in genome editing technology, featuring three principal effector proteins with distinct functionalities: Cas9, which induces site-specific double-strand breaks guided by a single guide RNA, enabling precise gene knockout and knock-in modifications; Cas12, which mediates targeted DNA cleavage through cis-activity while exhibiting nonspecific trans-cleavage of single-stranded DNA, a property exploited for ultrasensitive nucleic acid detection in molecular diagnostics; and Cas13, an RNA-guided RNase that specifically degrades complementary RNA transcripts, demonstrating significant potential for antiviral therapies and transcriptome regulation. Despite these advances, the clinical translation of CRISPR/Cas systems faces substantial challenges, particularly in achieving efficient and controllable delivery. This reviewsystematically examines current delivery modalities for CRISPR/Cas systems, with particular emphasis on the implementation of DNA-based functional materials as advanced delivery vehicles. The integration of multifunctional DNA nanostructures with diverse CRISPR/Cas systems may facilitate the development of integrated theranostic platforms, thereby advancing precision medicine through synergistic bioengineering approaches.