Advances in therapeutic bacterial antisense biotechnology

Abstract

Antisense therapeutics are a biotechnological form of antibiotic therapy using chemical analogues of short single-stranded nucleic acid sequences modified to form stable oligomers. These molecules are termed antisense oligonucleotides (ASOs) because their sequence is complementary, via Watson-Crick specific base pairing, to their target messenger RNA (mRNA). ASOs modify gene expression in this sequence-dependent manner by binding to its complementary mRNA and inhibiting its translation into protein through steric blockage and/or through RNase degradation of the ASO/RNA duplex. The widespread use of conventional antibiotics has led to the increasing emergence of multiple drug-resistant pathogenic bacteria. There is an urgent need to develop alternative therapeutic strategies to reduce the morbidity and mortality associated with bacterial infections, and until recently, the use of ASOs as therapeutic agents has been essentially limited to eukaryotic cells, with ASOs as antibacterials having been largely unexplored primarily due to the poor uptake efficiency of antisense molecules by bacteria. There are conceptual advantages to bacterial antisense antibiotic therapies, including a sequence-dependent approach that allows for a rational design to multiple specific molecular targets. This review summarizes the current knowledge of antisense bacterial biotechnology and highlights the recent progress and the current obstacles in their development for therapeutic applications.

Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations

“…Recently, strategy of oligonucleotide therapeutics was applied for acting on new therapeutic targets, for instance transcription, however due to undesirable physicochemical characteristics such as size, charge, and hydrophilicity that limit effective permeation across bacterial membranes to reach their target site, new strategies should be developed to solve the problem of efficient delivery of oligonucleotide therapeutics [185].…”

Nano-graphene oxide with antisense <i>vicR</i> RNA reduced exopolysaccharide synthesis and biofilm aggregation for <i>Streptococcus mutans </i>

“…However, few nucleic acid molecules or plasmids could enter bacterial cells without an effective vector. Therefore, there is a need to develop effective and relatively stable vectors which can deliver nucleic acid molecules 20) . In present study, a GO based antisense RNA transformation method has been developed using electrostatic interacted GO-PEI complexes loaded with recombinant pDL278 ASvicR plasmid vector.…”

Nucleic Acid Hybrids as Advanced Antibacterial Nanocarriers

“…The specificity of antisense oligonucleotide therapies to their mRNA targets and subsequent translational effects contributes to their success in inhibiting a wide range of bacteria genes that drive resistance or promote bacteria growth [129]. To address the poor stability of unmodified antisense oligonucleotides, antisense peptide nucleic acids are a new generation of DNA analogues, with improved stability stemming from their resistance to enzymatic degradation [130,131]. Nevertheless, similar to their unmodified sequences, entry into bacteria cells is challenging for many.…”