OAd.shDNMT1

OAd.shDNMT1 is an engineered oncolytic adenovirus that expresses a short hairpin RNA (shRNA) targeting DNA methyltransferase 1 (DNMT1). Developed by researchers at the University of Helsinki, this therapeutic candidate is designed to remodel the tumor microenvironment by downregulating DNMT1, which is often overexpressed in myeloid-derived suppressor cells (MDSCs) and contributes to their accumulation and suppressive function. The virus works through direct oncolysis and by generating shDNMT1-loaded small extracellular vesicles (sEVs) that are taken up by MDSCs, leading to their reduction. Preclinical studies in triple-negative breast cancer and colon carcinoma models have shown that OAd.shDNMT1 can enhance the efficacy of immune checkpoint inhibitors and promote systemic antitumor immunity.