Current updates of CRISPR/Cas9‐mediated genome editing and targeting within tumor cells: an innovative strategy of cancer management

Abstract

Clustered regularly interspaced short palindromic repeats-associated protein (CRISPR/Cas9), an adaptive microbial immune system, has been exploited as a robust, accurate, efficient and programmable method for genome targeting and editing. This innovative and revolutionary technique can play a significant role in animal modeling, in vivo genome therapy, engineered cell therapy, cancer diagnosis and treatment. The CRISPR/Cas9 endonuclease system targets a specific genomic locus by single guide RNA (sgRNA), forming a heteroduplex with target DNA. The Streptococcus pyogenes Cas9/sgRNA:DNA complex reveals a bilobed architecture with target recognition and nuclease lobes. CRISPR/Cas9 assembly can be hijacked, and its nanoformulation can be engineered as a delivery system for different clinical utilizations. However, the efficient and safe delivery of the CRISPR/Cas9 system to target tissues and cancer cells is very challenging, limiting its clinical utilization. Viral delivery strategies of this system may have many advantages, but disadvantages such as immune system stimulation, tumor promotion risk and small insertion size outweigh these advantages. Thus, there is a desperate need to develop an efficient non-viral physical delivery system based on simple nanoformulations. The delivery strategies of CRISPR/Cas9 by a nanoparticle-based system

Recent Advances in Genome-Editing Technology with CRISPR/Cas9 Variants and Stimuli-Responsive Targeting Approaches within Tumor Cells: A Future Perspective of Cancer Management

“…These lobes possess a positively charged groove at their interface to accommodate sgRNA:DNA heteroduplexes. The NUC lobe contains HNH and RuvC domains, whereas the REC lobe binds sgRNA and DNA heteroduplex [ 6 ]. Cas9 endonuclease forms a complex with either CRISPR RNA (crRNA) or trans-activating crRNA (tracrRNA).…”

“…In addition to genome editing, this system has been applied for transcriptional regulation, epigenetic modeling, and genome imaging. CRISPR/Cas9-based genome editing has emerged as a versatile tool for the study and treatment of diverse cancers [ 6 ]. With the help of the CRISPR/Cas9 system, precise manipulation of any DNA sequence is possible, defined by a short stretch of guide RNA (gRNA) [ 7 ].…”

Advanced strategies for CRISPR/Cas9 delivery and applications in gene editing, therapy, and cancer detection using nanoparticles and nanocarriers

“…16 Furthermore, Allemailem et al explored the structural understanding of the streptococcus pyogenic CRISPR/Cas9 system, offering insightful information about the intricate mechanistic workings of the system. 17…”

Biogenic materials for CRISPR delivery and therapeutics

“…The materials mainly include viruses and viroids, bacteria and bacteriaderived vesicles, cells and cell-derived vesicles, bioactive substances, etc. 15,16 The biogenic delivery vehicles of CRISPR/Cas system in vivo application are summarized in Fig. 1.…”