AI Article Synopsis
- - Recent research highlights the need for innovative cancer treatments, particularly through the use of oncolytic viruses (OVs) that can attack tumors in multiple ways.
- - The study discovers a specific amiRNA, called amiR-4, that enhances the effectiveness of a type of oncolytic virus, revealing ARID1A as a key factor in tumor resistance.
- - Combining virus targeting of ARID1A with small-molecule inhibitors like EZH2 leads to effective killing of both infected and uninfected cancer cells, suggesting a new therapeutic strategy involving amiRNA and traditional treatments.
Article Abstract
Recent advances in cancer therapeutics clearly demonstrate the need for innovative multiplex therapies that attack the tumour on multiple fronts. Oncolytic or "cancer-killing" viruses (OVs) represent up-and-coming multi-mechanistic immunotherapeutic drugs for the treatment of cancer. In this study, we perform an in-vitro screen based on virus-encoded artificial microRNAs (amiRNAs) and find that a unique amiRNA, herein termed amiR-4, confers a replicative advantage to the VSVΔ51 OV platform. Target validation of amiR-4 reveals ARID1A, a protein involved in chromatin remodelling, as an important player in resistance to OV replication. Virus-directed targeting of ARID1A coupled with small-molecule inhibition of the methyltransferase EZH2 leads to the synthetic lethal killing of both infected and uninfected tumour cells. The bystander killing of uninfected cells is mediated by intercellular transfer of extracellular vesicles carrying amiR-4 cargo. Altogether, our findings establish that OVs can serve as replicating vehicles for amiRNA therapeutics with the potential for combination with small molecule and immune checkpoint inhibitor therapy.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990073 | PMC |
| http://dx.doi.org/10.1038/s41467-022-29526-8 | DOI Listing |
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