CRISPR-Cas13 System as a Promising and Versatile Tool for Cancer Diagnosis, Therapy, and Research

Abstract

Over the past decades, significant progress has been made in targeted cancer therapy. In precision oncology, molecular profiling of cancer patients enables the use of targeted cancer therapeutics. However, current diagnostic methods for molecular analysis of cancer are costly and require sophisticated equipment. Moreover, targeted cancer therapeutics such as monoclonal antibodies and small-molecule drugs may cause off-target effects and they are available for only a minority of cancer driver proteins. Therefore, there is still a need for versatile, efficient, and precise tools for cancer diagnostics and targeted cancer treatment. In recent years, the CRISPR-based genome and transcriptome engineering toolbox has expanded rapidly. Particularly, the RNA-targeting CRISPR-Cas13 system has unique biochemical properties, making Cas13 a promising tool for cancer diagnosis, therapy, and research. Cas13-based diagnostic methods allow early detection and monitoring of cancer markers from liquid biopsy samples without the need for complex instrumentation. In addition, Cas13 can be used for targeted cancer therapy through degrading and manipulating cancer-associated transcripts with high efficiency and specificity. Moreover, Cas13-mediated programmable RNA manipulation tools offer invaluable opportunities for cancer research, identification of drug-resistance mechanisms, and discovery of novel therapeutic targets. Here, we review and discuss the current use and potential applications of the CRISPR-Cas13 system in cancer diagnosis, therapy, and research. Thus, researchers will gain a deep understanding of CRISPR-Cas13 technologies, which have the potential to be used as next-generation cancer diagnostics and therapeutics.

Designing libraries for pooled CRISPR functional screens of long noncoding RNAs

“…Similar to CRISPRi/a, Cas13 can be converted into a programmable RNA binding platform by mutating its catalytic site (dCas13) and fusing it to a catalytic enzyme with desired activities. In this way, dCas13 could be use, for example, as a tool for live cell RNA imaging (Palaz et al 2021 ). This may be a promising option for gene therapy applications, where DNA mutation is undesirable (Anton et al 2020 ).…”

Potential of the CRISPR‐Cas system for improved parasite diagnosis

“…[50] CRISPR-Cas13 has also been utilized for early detection and monitoring of cancer markers from clinical patient samples, for identification of drug-resistance mechanisms, and the discovery of novel therapeutic targets via degrading and manipulating cancer-associated transcripts with high efficiency and specificity. [51] A CRISPR-Cas13 based assay has also been developed to detect opportunistic infections post-transplantation and for the monitoring of transplant rejection [52] in order to improve long-term patient outcomes. Several CRISPRbased biosensing platforms have also been developed to detect specific microRNAs (miRNA), by combining LAMP/RPA with reverse transcriptase and other modifications to amplify sequences from miRNA.…”

An Outlook on Global Regulatory Landscape for Genome-Edited Crops

“…A further advantage is that temporary and reversible editing with CRISPR/Cas13 avoids the potential risks and ethical issues associated with permanent genome editing. RNA editing with CRISPR/Cas13 has opened up a new era for diagnostics, clinical, and therapeutic treatments [ 110 ].…”