{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["49(5)"],"submitter":["Akabane-Nakata M"],"funding":["Alnylam Pharmaceuticals"],"pubmed_abstract":["We recently reported the synthesis of 2'-fluorinated Northern-methanocarbacyclic (2'-F-NMC) nucleotides, which are based on a bicyclo[3.1.0]hexane scaffold. Here, we analyzed RNAi-mediated gene silencing activity in cell culture and demonstrated that a single incorporation of 2'-F-NMC within the guide or passenger strand of the tri-N-acetylgalactosamine-conjugated siRNA targeting mouse Ttr was generally well tolerated. Exceptions were incorporation of 2'-F-NMC into the guide strand at positions 1 and 2, which resulted in a loss of the in vitro activity. Activity at position 1 was recovered when the guide strand was modified with a 5' phosphate, suggesting that the 2'-F-NMC is a poor substrate for 5' kinases. In mice, the 2'-F-NMC-modified siRNAs had comparable RNAi potencies to the parent "],"journal":["Nucleic acids research"],"pagination":["2435-2449"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7969009"],"repository":["biostudies-literature"],"pubmed_title":["siRNAs containing 2'-fluorinated Northern-methanocarbacyclic (2'-F-NMC) nucleotides: in vitro and in vivo RNAi activity and inability of mitochondrial polymerases to incorporate 2'-F-NMC NTPs."],"pmcid":["PMC7969009"],"pubmed_authors":["Akabane-Nakata M","Erande ND","Janas MM","Mendez M","Matsuda S","Qin J","Woods LB","Kumar P","Gilbert JA","Jiang Y","Egli M","Schlegel MK","O'Flaherty DK","Manoharan M","Degaonkar R","Zlatev I"],"additional_accession":[]},"is_claimable":false,"name":"siRNAs containing 2'-fluorinated Northern-methanocarbacyclic (2'-F-NMC) nucleotides: in vitro and in vivo RNAi activity and inability of mitochondrial polymerases to incorporate 2'-F-NMC NTPs.","description":"We recently reported the synthesis of 2'-fluorinated Northern-methanocarbacyclic (2'-F-NMC) nucleotides, which are based on a bicyclo[3.1.0]hexane scaffold. Here, we analyzed RNAi-mediated gene silencing activity in cell culture and demonstrated that a single incorporation of 2'-F-NMC within the guide or passenger strand of the tri-N-acetylgalactosamine-conjugated siRNA targeting mouse Ttr was generally well tolerated. Exceptions were incorporation of 2'-F-NMC into the guide strand at positions 1 and 2, which resulted in a loss of the in vitro activity. Activity at position 1 was recovered when the guide strand was modified with a 5' phosphate, suggesting that the 2'-F-NMC is a poor substrate for 5' kinases. In mice, the 2'-F-NMC-modified siRNAs had comparable RNAi potencies to the parent ","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2026-05-01T17:25:35.222Z","creation":"2024-11-15T01:13:22.124Z"},"accession":"S-EPMC7969009","cross_references":{"pubmed":["33577685"],"doi":["10.1093/nar/gkab050"]}}