Multidimensional Engineering of CRISPR Systems— Synergistic Breakthroughs in Tool Innovation, Delivery Optimization, and Precise Regulation
Zhijing Hu · Theoretical and Natural Science · 2025
The CRISPR-Cas system has emerged as a revolutionary gene-editing technology, yet its clinical translation is constrained by off-target effects, suboptimal delivery efficiency, and limited adaptability across therapeutic contexts. This article presents a "multi-dimensional engineering" framework, systematically integrating the collaborative strategies of tool innovation, delivery optimization, and precise regulation to break through existing technical bottlenecks. In tool innovation, various regulatory tools have significantly improved editing accuracy and safety, reducing off-target activities. In the field of delivery systems, new universal delivery platforms have achieved the efficient and safe delivery of CRISPR components and enhanced tissue targeting. At the clinical translation level, CRISPR technology has been successfully applied in POC detection of infectious diseases, cancer immunotherapy, and the construction of genetic disease stem cell models. This article further explores the self-targeting repair mechanism of archaeal CRISPR systems to provide insights into precise regulation and proposes future directions to achieve a leap from the laboratory to the clinic.