A Novel Anti-Cancer Therapy: CRISPR/Cas9 Gene Editing

Abstract

Cancer becomes one of the main causes of human deaths in the world due to the high incidence and mortality rate and produces serious economic burdens. With more and more attention is paid on cancer, its therapies are getting more of a concern. Previous research has shown that the occurrence, progression, and treatment prognosis of malignant tumors are closely related to genetic and gene mutation. CRISPR/Cas9 has emerged as a powerful method for making changes to the genome, which has extensively been applied in various cell lines. Establishing the cell and animal models by CRISPR/Cas9 laid the foundation for the clinical trials which possibly treated the tumor. CRISPR-Cas9-mediated genome editing technology brings a great promise for inhibiting migration, invasion, and even treatment of tumor. However, the potential off-target effect limits its clinical application, and the effective ethical review is necessary. The article reviews the molecular mechanisms of CRISPR/Cas9 and discusses the research and the limitation related to cancer clinical trials.

Systemic delivery of specific and efficient CRISPR/Cas9 system targeting HPV16 oncogenes using LL‐37 antimicrobial peptide in C57BL/6 mice

“…However, the off-target effect and delivery with minimal systemic toxicity limit clinical applications. 52 With this knowledge, we tried to develop a targeted and safe gene editing of HPV16-associated tumors using CRISPR/Cas9 method in C57BL/6…”

“…The CRISPR/Cas technique brings great promise for inhibiting migration and invasion. However, the off‐target effect and delivery with minimal systemic toxicity limit clinical applications 52 . With this knowledge, we tried to develop a targeted and safe gene editing of HPV16‐associated tumors using CRISPR/Cas9 method in C57BL/6 mice, and explored the potential of using CPPs in systemic delivery of CRISPR/Cas9‐mediated therapies.…”

High-content CRISPR screening in tumor immunology

“…In recent years, CRISPR technology has been extended to the clinic ( 143 – 145 ) ( Figure 2D ). Initial proof-of-concept clinical trials in advanced esophageal (NCT03081715), metastatic non-small cell lung ( 146 ), and advanced, refractory cancer (NCT03399448) ( 147 ) have demonstrated CRISPR-Cas9 editing of autologous CAR T cells prior to adoptive transfer to be safe and feasible.…”

Bioorthogonal CRISPR/Cas9‐Drug Conjugate: A Combinatorial Nanomedicine Platform

“…[34,49] Although some previous studies have demonstrated systemic delivery of the CRISPR/Cas9 system to tumors based on conventional nano-formulations, the efficiency of delivering the RNPs, in general, has been extremely low. [50,51] In the clinic, intratumoral delivery has been a widely used route for adenovirus-based therapy. [52] Here, we show the efficacy of the ComBiNE platform through an intratumoral route, which can bring a substantial impact on cancer treatment in the clinic.…”