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Series GSE232819 Query DataSets for GSE232819
Status Public on Jul 11, 2023
Title A side-by-side comparison of peptide-delivered antisense antibiotics employing different nucleotide mimics
Organism Salmonella enterica subsp. enterica serovar Typhimurium
Experiment type Expression profiling by high throughput sequencing
Summary Antisense oligomer (ASO)-based antibiotics that target mRNAs of essential bacterial genes bear great potential in the fight against antimicrobial resistance and for precision microbiome editing. The development of such antisense antibiotics has primarily focused on using phosphoramidite morpholino (PMO) and peptide nucleic acid (PNA) backbones, largely ignoring the growing number of chemical modalities that have spurred the success of ASO-based therapy in general. Here, we compare seven chemically distinct 10mer-ASOs, all designed to target the same essential acpP mRNA upon delivery with a KFF-peptide carrier into Salmonella, comparing PNA, PMO, phosphorothioate modified-DNA (PTO), 2’-methoxylated RNA (RNA-OMe), 2’-methoxyethylated RNA (RNA-MOE), 2’-fluorinated RNA (RNA-F) and 2’-locked RNA (LNA). Our systematic analysis using a variety of in vitro and in vivo methods to evaluate ASO uptake, target pairing and bacterial killing suggests that only PNA and PMO make it into Salmonella to cause bacterial growth inhibition. However, given their high target binding and translational repression activity in vitro, ASOs based on LNA and RNA-MOE appear to be promising candidates for antisense antibiotics that will require the identification of an efficient carrier.
Overall design Comparative gene expression profiling analysis of RNA-seq data for Salmonella cells after 15 min exposure to several nucleotide mimics fused to the KFF pepide targeting the essential gene acpP. 2 replicates and 10 conditions
Contributor(s) Ghosh C, Popella L, Venugopalan D, Jung J, Barquist L, Höbartner C, Vogel J
Citation(s) 38413166
Submission date May 18, 2023
Last update date Jun 12, 2024
Contact name Jakob Jeremias Jung
Organization name University of Würzburg
Department Institute of Molecular Infection Biology (IMIB)
Lab Vogel lab
Street address Josef-Schneider-Str. 2/Bau D15
City Würzburg
State/province Bayern
ZIP/Postal code 97080
Country Germany
Platforms (1)
GPL21220 Illumina NextSeq 500 (Salmonella enterica subsp. enterica serovar Typhimurium)
Samples (20)
GSM7383857 Control_1
GSM7383860 RNA_MOE_1
GSM7383861 RNA_F_1
BioProject PRJNA974017

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GSE232819_counttable.tsv.gz 185.5 Kb (ftp)(http) TSV
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