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• W2178215900 endingPage "e48" @default.
• W2178215900 startingPage "e48" @default.
• W2178215900 abstract "Artificial microRNA (amiRNA) sequences embedded in natural microRNA (miRNA) backbones have proven to be useful tools for RNA interference (RNAi). amiRNAs have reduced off-target and toxic effects compared to other RNAi-based methods such as short-hairpin RNAs (shRNA). amiRNAs are often less effective for knockdown, however, compared to their shRNA counterparts. We screened a large empirically-designed amiRNA set in the synthetic inhibitory BIC/miR-155 RNA (SIBR) scaffold and show common structural and sequence-specific features associated with effective amiRNAs. We then introduced exogenous motifs into the basal stem region which increase amiRNA biogenesis and knockdown potency. We call this modified backbone the enhanced SIBR (eSIBR) scaffold. Using chained amiRNAs for multi-gene knockdown, we show that concatenation of miRNAs targeting different genes is itself sufficient for increased knockdown efficacy. Further, we show that eSIBR outperforms wild-type SIBR (wtSIBR) when amiRNAs are chained. Finally, we use a lentiviral expression system in cultured neurons, where we again find that eSIBR amiRNAs are more potent for multi-target knockdown of endogenous genes. eSIBR will be a valuable tool for RNAi approaches, especially for studies where knockdown of multiple targets is desired." @default.
• W2178215900 created "2016-06-24" @default.
• W2178215900 creator A5028389694 @default.
• W2178215900 creator A5047359105 @default.
• W2178215900 creator A5048781447 @default.
• W2178215900 creator A5064906223 @default.
• W2178215900 date "2015-11-17" @default.
• W2178215900 modified "2023-10-06" @default.
• W2178215900 title "Improved knockdown from artificial microRNAs in an enhanced miR-155 backbone: a designer's guide to potent multi-target RNAi" @default.
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• W2178215900 doi "https://doi.org/10.1093/nar/gkv1246" @default.
• W2178215900 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4797272" @default.
• W2178215900 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26582923" @default.
• W2178215900 hasPublicationYear "2015" @default.
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