A comparative analysis of peptide-delivered antisense antibiotics using diverse nucleotide mimics

TABLE 3.

Summary of the comparison between the different antisense oligomers

ASO modality mRNA hybridization (EMSA) Inhibition of translation in vitro Antibacterial activity (MIC, µM)a acpP depletion (RNA-seq)a AcpP protein reduction Outer membrane permeationa Uptake inside bacteria (MS)a
RNA-F ++ ++ >10
RNA-OMe >10
RNA-MOE ++ +++ >10
LNA +++ +++ >10
DNA-PTO >10
PMO + ++ 10 + + ++ +
PNA +++ +++ 1.25 ++ ++ ++ +
  • (ASO) Antisense oligomer, (EMSA) electrophoretic mobility shift assays, (MIC) minimum inhibitory concentration, (MS) mass-spectrometry, (RNA-F) 2′-fluorinated RNA, (RNA-OMe) 2′-methylated RNA, (RNA-MOE) 2′-methoxyethylated RNA, (LNA) 2′–4′-locked RNA, (PTO) phosphorothioate, (PMO) phosphorodiamidate morpholino, (PNA) peptide nucleic acid.

  • aThe ASO was conjugated to the carrier peptide. Effect strength is represented by additional (+) signs.

This Article

  1. RNA 30: 624-643