New Therapeutics for Extracellular Vesicles: Delivering CRISPR for Cancer Treatment

Abstract

Cancers are defined by genetic defects, which underlines the prospect of using gene therapy in patient care. During the past decade, CRISPR technology has rapidly evolved into a powerful gene editing tool with high fidelity and precision. However, one of the impediments slowing down the clinical translation of CRISPR-based gene therapy concerns the lack of ideal delivery vectors. Extracellular vesicles (EVs) are nano-sized membrane sacs naturally released from nearly all types of cells. Although EVs are secreted for bio-information conveyance among cells or tissues, they have been recognized as superior vectors for drug or gene delivery. Recently, emerging evidence has spotlighted EVs in CRISPR delivery towards cancer treatment. In this review, we briefly introduce the biology and function of the CRISPR system and follow this with a summary of current delivery methods for CRISPR applications. We emphasize the recent progress in EV-mediated CRISPR editing for various cancer types and target genes. The reported strategies for constructing EV-CRISPR vectors, as well as their limitations, are discussed in detail. The review aims to throw light on the clinical potential of engineered EVs and encourage the expansion of our available toolkit to defeat cancer.

CRISPR/Cas gene editing and delivery systems for cancer therapy

“…At present, accumulating evidence has indicated EVs possess the ability of loading biomolecules and traveling across physiologic barriers to target specific cells or tissues (Dixson et al, 2023; Wu, Fu, et al, 2023). So EVs are recognized as the potential selective delivery vehicles for various cargoes including CRISPR/Cas systems (Wang, Wang, et al, 2023; Yan & Liang, 2022). Based on the size and biogenesis, there are three types of EVs: exosomes, microvesicles, and apoptotic vesicles (Jeppesen et al, 2023; Rädler et al, 2023; Szatanek et al, 2017).…”

Global research trends in CRISPR-related technologies associated with extracellular vesicles from 2015 to 2022: a bibliometric, dynamic, and visualized study

“…Cas9-based target screening provides an advanced method for better understanding of many diseases. However, owing to the off-target effect, administration challenges, limitations, and immunogenicity, further clinical application of CRISPR is hindered [ 65 ]. Although EVs have potential for delivering CRPSIR/Cas products, owing to source issues, many EV biomacromolecules have the potential to affect cellular physiological functions, such as tumor-derived EVs, which may lead to tumor development and metastasis [ 66 ].…”

Extracellular Vesicle-Based SARS-CoV-2 Vaccine

“…Therefore, it is necessary to develop a method for efficient delivery to target tissues by enhancing the targeting ability of EVs. To date, approaches such as endogenous modification using biosynthetic processes, including genetic engineering and metabolic labelling, have been proposed [ 147 , 148 , 149 ]. However, endogenous modifications may affect cell function, and the properties of EVs may change from the original.…”