microRNA-181a silencing by antisense oligonucleotides delivered by virus-like particles
| Autor: | Soo Khim Chan, Nicole F. Steinmetz |
|---|---|
| Rok vydání: | 2023 |
| Předmět: |
Ovarian Neoplasms
Oligonucleotides Biomedical Engineering Antagomirs Gene Therapy General Chemistry General Medicine Small Interfering Article Ovarian Cancer Macromolecular and Materials Chemistry MicroRNAs Rare Diseases Genetics Humans RNA Female General Materials Science Antisense Biotechnology Cancer |
| Zdroj: | Journal of materials chemistry. B, vol 11, iss 4 J Mater Chem B |
| ISSN: | 2050-7518 2050-750X |
| DOI: | 10.1039/d2tb02199d |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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