2026-04-17T12:12:22Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1794182025-12-04T21:41:44Zcom_2072_1057col_2072_478917col_2072_478933

00925njm 22002777a 4500 dc Alagia, Adele author Terrazas Martínez, Montserrat author Eritja i Casadellà, Ramon author 2021-07-27T06:58:57Z 2021-07-27T06:58:57Z 2014-11-04 2021-07-27T06:58:57Z The RNA interference pathway (RNAi) is a specific and powerful biological process, triggered by small non-coding RNA molecules and involved in gene expression regulation. In this work, we explored the possibility of increasing the biological stability of these RNA molecules by replacing their natural ribose ring with an acyclic L-threoninol backbone. In particular, this modification has been incorporated at certain positions of the oligonucleotide strands and its effects on the biological properties of the siRNA have been evaluated. In vitro cellular RNAi assays have demonstrated that the L-threoninol backbone is well tolerated by the RNAi machinery in both double and single-stranded fashion, with activities significantly higher than those evinced by the unmodified RNAs and comparable to the well-known phosphorothioate modification. Additionally, this modification conferred extremely strong resistance to serum and 3'/5'-exonucleases. In view of these results, we applied this modification to the knockdown of a therapeutically relevant human gene such as apolipoprotein B (ApoB). Further studies on the activation of the innate immune system showed that L-threoninol-modified RNAs are slightly less stimulatory than unmodified RNAs. RNA Regulació genètica Oligonucleòtids Apoproteïnes RNA Genetic regulation Oligonucleotides Apolipoproteins RANA/aTNA chimeras: RNAi effects and nuclease resistance of single and double-stranded RNAs