An Update on the Application of CRISPR Technology in Clinical Practice

Abstract

The CRISPR/Cas system, an innovative gene-editing tool, is emerging as a promising technique for genome modifications. This straightforward technique was created based on the prokaryotic adaptive immune defense mechanism and employed in the studies on human diseases that proved enormous therapeutic potential. A genetically unique patient mutation in the process of gene therapy can be corrected by the CRISPR method to treat diseases that traditional methods were unable to cure. However, introduction of CRISPR/Cas9 into the clinic will be challenging because we still need to improve the technology's effectiveness, precision, and applications. In this review, we first describe the function and applications of the CRISPR–Cas9 system. We next delineate how this technology could be utilized for gene therapy of various human disorders, including cancer and infectious diseases and highlight the promising examples in the field. Finally, we document current challenges and the potential solutions to overcome these obstacles for the effective use of CRISPR–Cas9 in clinical practice.

In-uterorescue of neurological dysfunction in a mouse model of Wiedemann-Steiner syndrome

“…Genetic disorders are being diagnosed earlier than before with the onset of whole genome sequencing and exome sequencing [33] and there is an explosion of strategies that have successfully made it to the clinic including small molecules, ASO-based strategies and CRISPR-Cas9 based strategies [34], [35]. Using a genetically based strategy to examine the likelihood, the window of opportunity, and which aspects of the phenotype are malleable could be of great value for prioritizing any Mendelian disorder for therapeutic development as well as offering an excellent genetic control for such studies.…”

Genome editing and cancer therapy: handling the hypoxia-responsive pathway as a promising strategy

“…Importantly, lipid nanoparticles were employed for the delivery [ 180 , 181 ]. In the cynomolgus monkey report, the ABE approach (using ABE 8.8 mRNA) was used to alter splice donor at the boundary of PCSK9 exon 1 and intron 1 with an efficiency of about 50% editing in the liver [ 182 ]. A similar methodology was used in the macaques' study (i.e., lipid nanoparticles, ABE mRNA, and a splicing acceptor as target) [ 181 ].…”

“…Investigations into the use of genome editing in cancer treatment are so far much more limited than in genetic diseases therapy. As a result, there is scarce conclusive data from clinical trials [ 182 ]. Indeed, there are limits not yet overcome and on which scientific efforts have focused in recent years, such as improvement of delivery methods, off- targeting, the unsolicited generation of mutations in the p53 gene, the immunogenicity of CRISPR-Cas9 systems and, not less important, the ethical requirement.…”

Therapeutic In Vivo Gene Editing Achieved by a Hypercompact CRISPR‐Cas12f1 System Delivered with All‐in‐One Adeno‐Associated Virus

“…[ 3 ] Among them, Cas9 and Cas12a nucleases are the most prevalent and have already been employed in gene therapy to treat genetic diseases and cancer. [ 4 , 5 ]…”