Nano-vectors for CRISPR/Cas9-mediated genome editing
Peng Yang, Athena Yue-Tung Lee, Jingjing Xue, Shih‐Jie Chou, Calvin Lee, Patrick Tseng, Tiffany X. Zhang, Yazhen Zhu, Junseok Lee, Shih‐Hwa Chiou, Hsian‐Rong Tseng
Abstract
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) genome editing system has revolutionized the field of genome editing for therapeutic applications for genetic diseases and cancers, the development of disease models, identification of targets for drug development. However, safe and efficient delivery of the CRISPR/Cas9 genome editing system in vivo remains a significant challenge. Compared to viral vectors, non-viral nano-vectors have the following advantages: cost-effective, scale-up production, ease of chemical modification, large packaging capacity, lower immunogenicity, better protection of CRISPR/Cas9 genome edition system from degradation in vivo. This comprehensive Review article highlights the recent advances in delivering the three categories of CRISPR/Cas9 genome editing cargoes (i.e., Cas9 DNA plasmid, Cas9 mRNA, and Cas9 ribonucleoprotein) by using three types of nano-vectors: lipid-based, polymer-based, and polymer inorganic nano-vectors to treat cancers and genetic diseases via two major gene-editing pathways: non-homologous end joining pathway and homology-directed repair pathway. This article also notes the therapeutic applications for treating cancers and genetic diseases, provides insights into the challenges of nano-vectors for the delivery of the CRISPR/Cas9 genome editing system and proposes promising strategies in future development, especially in the final clinical translation.