Issue 4, 2023

microRNA-181a silencing by antisense oligonucleotides delivered by virus-like particles

Abstract

Cowpea chlorotic mottle virus (CCMV) is a positive-sense RNA virus that can be repurposed for gene delivery applications. Understanding the self-assembly process of the virus enabled to remove its genome and replace it with desired nucleic acids, and we and others have previously reported using CCMV virus-like particle (VLP) to encapsulate siRNA, mRNA, as well as CpG oligodeoxynucleotides. In this study, the CCMV VLP was applied to encapsulate two different formats of anti-miR-181a oligonucleotides: naked RNA and chemically stabilized RNA to knockdown highly regulated miR-181a in ovarian cancer cells. miR-181a expression in ovarian tumors is associated with high aggressiveness, invasiveness, resistance to chemotherapy, and overall poor prognosis. Therefore, miR-181a is an important target for ovarian cancer therapy. qPCR data and cancer cell migration assays demonstrated higher knockdown efficacy when anti-miR-181a oligonucleotides were encapsulated and delivered using the VLPs resulting in reduced cancer cell invasiveness. Importantly, delivery of anti-miR-181a oligonucleotide into cells could be achieved without the aid of a transfection agent or surface modification. These results highlight the opportunity of plant-derived VLPs as nucleic acid carriers.

Graphical abstract: microRNA-181a silencing by antisense oligonucleotides delivered by virus-like particles

Article information

Article type
Paper
Submitted
13 10 2022
Accepted
17 12 2022
First published
04 1 2023

J. Mater. Chem. B, 2023,11, 816-825

microRNA-181a silencing by antisense oligonucleotides delivered by virus-like particles

S. K. Chan and N. F. Steinmetz, J. Mater. Chem. B, 2023, 11, 816 DOI: 10.1039/D2TB02199D

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