Development of delivery strategies for CRISPR-Cas9 genome editing

The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-related protein 9 (Cas9) genome editing system has attracted much attention due to its powerful genome editing capacity. However, CRISPR-Cas9 components are easily degraded by acids, enzymes, and other substances in the body fluids after entering the organism, thus efficiently delivering the CRISPR-Cas9 system into targeted organs or cells has been a central theme for promoting the application of CRISPR-Cas9 technology. Although several physical methods and viral vectors have been developed for CRISPR-Cas9 delivery, their clinical application still suffers from disadvantages, such as the risks of mutagenesis, cell damage, and poor specificity. As an alternative, non-viral nanocarriers hold great promise for circumventing these challenges. Furthermore, with aim to realize more efficient and precise genome editing and reduce the undesirable side effects, stimuli-responsive nanocarriers are designed for the spatiotemporal CRISPR-Cas9 delivery in responsive to various stimuli. In this review, we will summarize the recent progress in delivery strategies for CRISPR-Cas9 genome editing. The mechanisms and advantages of these strategies were reviewed, providing a comprehensive review of the rational design of materials and techniques for efficient and precise genome editing. At last, the potential challenges of current CRISPR-Cas9 delivery are discussed.