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Lipid and Carbohydrate Modifications Enhance Potency of Antisense Oligonucleotides Targeting Oncogenic KRAS
Faith Kivunga1, Virginie Baylot1, Julien Verget1
1ARNA, INSERM U1212, CNRS 5320, Université de Bordeaux, Bordeaux, F-33076, France.
Abstract:
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.
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