CRISPR/Cas9-based application for cancer therapy: Challenges and solutions for non-viral delivery

• Published in: Journal of controlled release Vol. 361; pp. 727 - 749
• Main Authors: Lin, Ying-Qi, Feng, Ke-Ke, Lu, Jie-Ying, Le, Jing-Qing, Li, Wu-Lin, Zhang, Bing-Chen, Li, Cheng-Lei, Song, Xun-Huan, Tong, Ling-Wu, Shao, Jing-Wei
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.09.2023
• Subjects: cancer therapy; carcinogenicity; CRISPR-Cas systems; CRISPR/Cas9; editing efficient; genes; immunogenicity; neoplasms; Non-viral vectors; virus transmission; viruses; cancer therapy; Non-viral vectors; CRISPR/Cas9; editing efficient
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2023.08.028

CRISPR/Cas9 genome editing is a promising therapeutic technique, which makes precise and rapid gene editing technology possible on account of its high sensitivity and efficiency. CRISPR/Cas9 system has been proved to able to effectively disrupt and modify genes, which shows great potential for cancer treatment. Current researches proves that virus vectors are capable of effectively delivering the CRISPR/Cas9 system, but immunogenicity and carcinogenicity caused by virus transmission still trigger serious consequences. Therefore, the greatest challenge of CRISPR/Cas9 for cancer therapy lies on how to deliver it to the target tumor site safely and effectively. Non-viral delivery systems with specific targeting, high loading capacity, and low immune toxicity are more suitable than viral vectors, which limited by uncontrollable side effects. Their medical advances and applications have been widely concerned. Herein, we present the molecule mechanism and different construction strategies of CRISPR/Cas9 system for editing genes at the beginning of this research. Subsequently, several common CRISPR/Cas9 non-viral deliveries for cancer treatment are introduced. Lastly, based on the main factors limiting the delivery efficiency of non-viral vectors proposed in the existing researches and literature, we summarize and discuss the main methods to solve these limitations in the existing tumor treatment system, aiming to introduce further optimization and innovation of the CRISPR/Cas9 non-viral delivery system suitable for cancer treatment. [Display omitted] •Qualities of non-viral vectors and anti-tumor effects for CRISPR/Cas9 delivery.•Breaking physiological barrier to improve gene editing efficiency.•Rationally design CRISPR/Cas9 releasing mechanism applicable to tumor site.•Enhanced anti-tumor efficacy through carrier modification.•Application of CRISPR/Cas9 in tumor therapy and current status of clinical treatment.