Customer Publication
Modified Nucleotides in Bifunctional Antisense Oligonucleotides: Exploring their Anticancer Potential
Journal: ChemMedChem (2025)
Research Areas: Cancer Research
Cell Lines: SKOV-3 (ovarian cancer cell)
Summary: This study investigates how different chemically modified nucleotides affect the performance of bifunctional antisense oligonucleotides (BASOs), which are designed to regulate alternative splicing of the PKM gene, a key metabolic switch often exploited by cancer cells. The researchers tested a wide range of nucleotide modifications to determine which best enhance BASO activity, both in shifting splicing toward the antitumor PKM1 isoform and in reducing cancer-like behaviors such as proliferation and motility. Using the HoloMonitor M4, they continuously tracked cell proliferation and movement in real time, revealing that several modifications not only maintained splicing regulatory activity but also significantly inhibited cancer cell proliferation and migration. Some modifications (e.g., phosphorothioates, s2U, FANA) caused strong antiproliferative or cytotoxic effects independently of splicing changes, showing that BASOs can act through multiple anticancer mechanisms. Overall, the study identifies modified BASOs with promising therapeutic potential and highlights that splicing correction alone does not fully explain their anticancer effects.