Peptide nucleic acid, the state-of-the-art toll for study and control of bacterial infections
Subject Areas : Bacteriology
Hanar Narenji
1
,
Hossein Samadi Kafil
2
*
1 - Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
2 - Drug Applied Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Keywords: Peptide nucleic acids, gene knock down, Antibiotic resistance.,
Abstract :
The increasing emergence of antibiotic-resistant bacteria, coupled with the slow development of new therapeutic alternatives, underscores the urgent need for novel strategies to combat these pathogens. Peptide nucleic acids (PNAs) are synthetic molecules capable of binding to DNA and RNA, making them useful for a variety of applications, including gene expression inhibition and gene knockdown to suppress bacterial growth. To effectively target a selected gene, it is crucial to choose a homologous sequence with the highest activity, and the PNA sequence must be tailored to the characteristics of the target gene. By targeting conserved genes within a specific genus, it is possible to inhibit the growth of a broad spectrum of pathogens. This study reviews researchs that have successfully achieved gene knockdown and bacterial growth inhibition. The findings offer a new perspective on therapeutic strategies, however, further investigations into the immunological responses, toxicity, and pharmacokinetics of PNAs are essential for their clinical application. Indeed, PNA could be used as a potential therapeutic option in future clinical applications.
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1. Carson LM, Watson EE. Peptide Nucleic Acids: From Origami to Editing. Chempluschem. 2024;89(11):23.
2. Abbasi s, Emtiazi G. Antimicrobial peptides of haloarchaea: Properties and applications of halocin. Journal of Microbial World. 2022;15(51):88-108.
3. Good L, Nielsen PE. Peptide nucleic acid (PNA) antisense effects in Escherichia coli. Curr Issues Mol Biol. 1999;1(1-2):111-6.
4. Jirakittiwut N, Sathianpitayakul P, Santanirand P, Akeda Y, Vilaivan T, Ratthawongjirakul P. Peptide nucleic acid-immobilised paper combined with multiplex recombinase polymerase amplification for the ultrasensitive and rapid detection of rifampicin-resistant tuberculosis. Sci Rep. 2025;15(1):025-86691.
5. Liang S, He Y, Xia Y, Wang H, Wang L, Gao R, et al. Inhibiting the growth of methicillin-resistant Staphylococcus aureus in vitro with antisense peptide nucleic acid conjugates targeting the ftsZ gene. Int J Infect Dis. 2015 1//;30:1-6.
6. Sannigrahi A, De N, Bhunia D, Bhadra J. Peptide nucleic acids: Recent advancements and future opportunities in biomedical applications. Bioorg Chem. 2025;155(108146):10.
7. Narenji H, Gholizadeh P, Aghazadeh M, Rezaee MA, Asgharzadeh M, Kafil HS. Peptide nucleic acids (PNAs): currently potential bactericidal agents. Biomed Pharmacother. 2017;93:580-8.
8. Narenji H, Gholizadeh P, Aghazadeh M, Rezaee MA, Asgharzadeh M, Kafil HS. Peptide nucleic acids (PNAs): currently potential bactericidal agents. Biomed Pharmacother. 2017;93:580-8.
9. Bai H, Sang G, You Y, Xue X, Zhou Y, Hou Z, et al. Targeting RNA polymerase primary σ70 as a therapeutic strategy against methicillin-resistant Staphylococcus aureus by antisense peptide nucleic acid. PLoS One. 2012;7(1).
10. Greenberg DE, Marshall-Batty KR, Brinster LR, Zarember KA, Shaw PA, Mellbye BL, et al. Antisense phosphorodiamidate morpholino oligomers targeted to an essential gene inhibit Burkholderia cepacia complex. The Journal of infectious diseases. 2010;201(12):1822-30.
11. Egholm M, Buchardt O, Christensen L, Behrens C, Freier SM, Driver DA, et al. PNA hybridizes to complementary oligonucleotides obeying the Watson–Crick hydrogen-bonding rules. Nature. 1993;365(6446):566-8.
12. Egholm M, Buchardt O, Nielsen PE, Berg RH. Peptide nucleic acids (PNA). Oligonucleotide analogs with an achiral peptide backbone. J Am Chem Soc. 1992;114(5):1895-7.
13. Demidov V, Frank-Kamenetskii MD, Egholm M, Buchardt O, Nielsen PE. Sequence selective double strand DNA cleavage by peptide nucleic acid (PNA) targeting using nuclease S1. Nucleic Acids Res. 1993;21(9):2103-7.
14. Egholm M, Christensen L, Deuholm KL, Buchardt O, Coull J, Nielsen PE. Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA. Nucleic Acids Res. 1995;23(2):217-22.
15. Patenge N, Pappesch R, Krawack F, Walda C, Mraheil MA, Jacob A, et al. Inhibition of growth and gene expression by PNA-peptide conjugates in Streptococcus pyogenes. Molecular Therapy-Nucleic Acids. 2013;2:e132.
16. Wierzba AJ, Richards EM, Lennon SR, Batey RT, Palmer AE. Unveiling the promise of peptide nucleic acids as functional linkers for an RNA imaging platform. RSC Chem Biol. 2024;6(2):249-62.
17. Hanvey JC, Peffer NJ, Bisi JE, Thomson SA, Cadilla R, Josey JA, et al. Antisense and antigene properties of peptide nucleic acids. Science. 1992;258(5087):1481-5.
18. Møllegaard NE, Buchardt O, Egholm M, Nielsen PE. Peptide nucleic acid. DNA strand displacement loops as artificial transcription promoters. Proceedings of the National Academy of Sciences. 1994;91(9):3892-5.
19. Soofi MA, Seleem MN. Targeting essential genes in Salmonella enterica serovar typhimurium with antisense peptide nucleic acid. Antimicrobial agents and chemotherapy. 2012;56(12):6407-9.
20. Farshineh Saei S, Baskevics V, Katkevics M, Rozners E. Recognition of Noncanonical RNA Base Pairs Using Triplex-Forming Peptide Nucleic Acids. ACS Chem Biol. 2025;20(1):179-85.
21. Koziel J, Maciag-Gudowska A, Mikolajczyk T, Bzowska M, Sturdevant DE, Whitney AR, et al. Phagocytosis of Staphylococcus aureus by macrophages exerts cytoprotective effects manifested by the upregulation of antiapoptotic factors. PLoS One. 2009;4(4):e5210.
22. D'Andrea LD, Romanelli A. Morphology and Applications of Self-Assembled Peptide Nucleic Acids. Int J Mol Sci. 2024;25(22).
23. Giancola JB, Raines RT. Endosomolytic peptides enable the cellular delivery of peptide nucleic acids. Chem Commun. 2024;60(100):15019-22.
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