One prominent open question in the field of antisense oligonucleotide remains the intracellular delivery of active sequences. While different strategies have been developed for addressing this issue, including formulation and/or conjugation approaches, multiconjugations with both sugars and nucleolipids have not been investigated so far. In this contribution, we are interested in a new hypothesis that focuses on the double conjugation of oligonucleotides with both glucose-thymine and nucleolipid moieties. The lipid carbohydrate modified antisense oligonucleotides were the most efficient in down regulating the expression of KRAS in pancreatic cancer cells.
Kivunga et al. (2026) studied this question.