siRNA design against DNMT1 overexpressed in triple-negative breast cancer patients

Triple-negative breast cancer (TNBC) lacks targeted therapies, this is due to the absence of estrogen, progesterone, and HER2 receptors, making it necessary to develop alternative approaches for the treatment of the disease. Therefore, in this article a comprehensive computational strategy was developed to design siRNA therapeutics targeting an oncogene, DNMT1 upregulated in TNBC patients. DNMT1 plays several roles in the development of tumors in TNBC cancer. siRNAs were designed to target DNMT1 mRNA and verified for their in-silico specificity, secondary structure stability, target binding, and activity profiling. Among the five siRNAs, one of the siRNA candidates showed a high predicted efficacy score and favorable docking interactions with the human AGO2 protein. Overall, this in-silico approach was successful in identifying a promising siRNA therapeutic candidate for targeting DNMT1 and potentially inhibiting TNBC through RNA interference.