Abstract
mRNA-driven CRISPR-Cas9 gene therapies have garnered widespread attention due to their ability to maintain highly efficient editing activity while preventing integration into the host cell genome. However, the widespread clinical application of mRNA-driven CRISPR-Cas9 gene therapy is limited by mRNA instability, strong immune responses, a short half-life, inefficient delivery in vivo, and off-target effects. This review summarizes recent advancements in efforts to enhance mRNA stability and translation efficiency, and it describes novel delivery vectors currently being used for mRNA-driven CRISPR-Cas9 therapies. Moreover, the development of novel gene editors based on CRISPR-Cas9 engineering and the development of length fragment integration technology based on prime editing tool engineering are also discussed. The discussion of these advances aims to provide a full picture of the challenges of mRNA-based CRISPR-Cas9 therapeutics for the treatment of various diseases.