Promising strategies employing nucleic acids as antimicrobial drugs

Luís Moreira; Nuno M Guimarães; Rita S Santos; Joana A Loureiro; Maria C Pereira; Nuno F Azevedo

doi:10.1016/j.omtn.2024.102122

Promising strategies employing nucleic acids as antimicrobial drugs

Mol Ther Nucleic Acids. 2024 Jan 18;35(1):102122. doi: 10.1016/j.omtn.2024.102122. eCollection 2024 Mar 12.

Authors

Luís Moreira^{1

2}, Nuno M Guimarães^{1

2}, Rita S Santos^{1

2}, Joana A Loureiro^{1

2}, Maria C Pereira^{1

2}, Nuno F Azevedo^{1

2}

Affiliations

¹ LEPABE-Laboratory for Process Engineering, Environment, Biotechnology, and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
² ALiCE-Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.

Abstract

Antimicrobial resistance (AMR) is a growing concern because it causes microorganisms to develop resistance to drugs commonly used to treat infections. This results in increased difficulty in treating infections, leading to higher mortality rates and significant economic effects. Investing in new antimicrobial agents is, therefore, necessary to prevent and control AMR. Antimicrobial nucleic acids have arisen as potential key players in novel therapies for AMR infections. They have been designed to serve as antimicrobials and to act as adjuvants to conventional antibiotics or to inhibit virulent mechanisms. This new category of antimicrobial drugs consists of antisense oligonucleotides and oligomers, DNAzymes, and transcription factor decoys, differing in terms of structure, target molecules, and mechanisms of action. They are synthesized using nucleic acid analogs to enhance their resistance to nucleases. Because bacterial envelopes are generally impermeable to oligonucleotides, delivery into the cytoplasm typically requires the assistance of nanocarriers, which can affect their therapeutic potency. Given that numerous factors contribute to the success of these antimicrobial drugs, this review aims to provide a summary of the key advancements in the use of oligonucleotides for treating bacterial infections. Their mechanisms of action and the impact of factors such as nucleic acid design, target sequence, and nanocarriers on the antimicrobial potency are discussed.

Keywords: DNAzymes; MT: Oligonucleotides: Therapies and Applications; antisense oligonucleotides and oligomers; bacteria; nanocarriers; nucleic acid analogs; transcription factor decoy.

Publication types

Review