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• W4319337296 abstract "Antisense oligomers (ASOs), such as peptide nucleic acids (PNAs), designed to inhibit the translation of essential bacterial genes, have emerged as attractive sequence- and species-specific programmable RNA antibiotics. Yet, potential drawbacks include unwanted side effects caused by their binding to transcripts other than the intended target. To facilitate the design of PNAs with minimal off-target effects, we developed MASON ( m ake a nti s ense o ligomers n ow), a web server for the design of PNAs that target bacterial mRNAs. MASON generates PNA sequences complementary to the translational start site of a bacterial gene of interest and reports critical sequence attributes and potential off-target sites. We based MASON's off-target predictions on experiments in which we treated Salmonella enterica serovar Typhimurium with a series of 10-mer PNAs derived from a PNA targeting the essential gene acpP but carrying two serial mismatches. Growth inhibition and RNA-sequencing (RNA-seq) data revealed that PNAs with terminal mismatches are still able to target acpP , suggesting wider off-target effects than anticipated. Comparison of these results to an RNA-seq data set from uropathogenic Escherichia coli (UPEC) treated with eleven different PNAs confirmed that our findings are not unique to Salmonella . We believe that MASON's off-target assessment will improve the design of specific PNAs and other ASOs." @default.
• W4319337296 created "2023-02-08" @default.
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• W4319337296 date "2023-02-07" @default.
• W4319337296 modified "2023-09-27" @default.
• W4319337296 title "Design and off-target prediction for antisense oligomers targeting bacterial mRNAs with the MASON web server" @default.
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• W4319337296 doi "https://doi.org/10.1261/rna.079263.122" @default.
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