Targeting miRNA by CRISPR/Cas in cancer: advantages and challenges

Abstract

Clustered regulatory interspaced short palindromic repeats (CRISPR) has changed biomedical research and provided entirely new models to analyze every aspect of biomedical sciences during the last decade. In the study of cancer, the CRISPR/CRISPR-associated protein (Cas) system opens new avenues into issues that were once unknown in our knowledge of the noncoding genome, tumor heterogeneity, and precision medicines. CRISPR/Cas-based gene-editing technology now allows for the precise and permanent targeting of mutations and provides an opportunity to target small non-coding RNAs such as microRNAs (miRNAs). However, the development of effective and safe cancer gene editing therapy is highly dependent on proper design to be innocuous to normal cells and prevent introducing other abnormalities. This study aims to highlight the cutting-edge approaches in cancer-gene editing therapy based on the CRISPR/Cas technology to target miRNAs in cancer therapy. Furthermore, we highlight the potential challenges in CRISPR/Cas-mediated miRNA gene editing and offer advanced strategies to overcome them.

Functions of Differentially Regulated miRNAs in Breast Cancer Progression: Potential Markers for Early Detection and Candidates for Therapy

“…To inhibit miRNA activity, small-molecule inhibitors specific to certain miRNAs are also being developed. The second strategy, miRNA replacement, includes the reintroduction of tumor-suppressor miRNA mimics to restore the loss of function [ 149 , 150 , 151 , 152 ].…”

“…Synthetic miRNA mimics must be delivered efficiently for target cells for miRNA replacement therapy to be effective. There are a variety of delivery systems that can be used to ensure effective uptake by target tissues, including viral vectors, lipid nanoparticles, and other nanocarriers [ 150 , 151 , 152 , 170 ]. A synthetic miRNA mimic is incorporated into the RISC and acts similarly to endogenous miRNAs once inside a cell.…”

Nanotechnology-based non-viral vectors for gene delivery in cardiovascular diseases

“…Liposomes have many merits as gene delivery vectors. Firstly, liposomes are spherical vesicles that encapsulate nucleic acids and resist nucleases ( Hussen and Mahmud, 2023 ). Secondly, similar to cell membranes, liposomes are easy to fuse with recipient cells and have high transfection efficiency.…”

Deciphering roles of protein post-translational modifications in IgA nephropathy progression and potential therapy

“…It is known that miRNAs belong to short, noncoding RNAs and modulate the gene expression [62]. Clearly, miRNAs have been reported to be involved in various diseases, including cancer [63][64][65]. One study showed that 37 miRNAs were differentially expressed in IgAN patients compared with healthy controls [66].…”