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Cardiolipin-Based Lipopolyplex Platform for the Delivery of Diverse Nucleic Acids into Gram-Negative Bacteria

1
Centre de Biophysique Moléculaire, UPR4301 CNRS, Rue Charles Sadron Orléans CEDEX 02, France
2
Unité INSERM 1078, Faculté de Médecine, Université de Bretagne Occidentale, Université Européenne de Bretagne, 22 avenue Camille Desmoulins, 29238 Brest CEDEX 3, France
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2019, 12(2), 81; https://doi.org/10.3390/ph12020081
Received: 30 April 2019 / Revised: 20 May 2019 / Accepted: 24 May 2019 / Published: 28 May 2019
(This article belongs to the Special Issue New Tools for Medicinal Chemists)
PDF [853 KB, uploaded 28 May 2019]
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Abstract

Antibiotic resistance is a growing public health concern. Because only a few novel classes of antibiotics have been developed in the last 40 years, such as the class of oxazolidinones, new antibacterial strategies are urgently needed [1]. Nucleic acid-based antibiotics are a new type of antimicrobials. However, free nucleic acids cannot spontaneously cross the bacterial cell wall and membrane;consequently, their intracellular delivery into bacteria needs to be assisted. Here, we introduce an original lipopolyplex system named liposome polymer nucleic acid (LPN), capable of versatile nucleic acid delivery into bacteria. We characterized LPN formed with significant therapeutic nucleic acids: 11 nt antisense single-stranded (ss) DNA and double-stranded (ds) DNA of 15 and 95 base pairs (bp), 9 kbp plasmid DNA (pDNA), and 1,000 nt ssRNA. All these complexes were efficiently internalized by two different bacterial species, i.e., Escherichia coli and Pseudomonas aeruginosa, as shown by flow cytometry. Consistent with intracellular delivery, LPN prepared with an antisense oligonucleotide and directed against an essential gene, induced specific and important bacterial growth inhibition likely leading to a bactericidal effect. Our findings indicate that LPN is a versatile platform for efficient delivery of diverse nucleic acids into Gram-negative bacteria.
Keywords: bacterial delivery; oligonucleotide; RNA; pDNA; ssDNA; dsDNA bacterial delivery; oligonucleotide; RNA; pDNA; ssDNA; dsDNA
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Perche, F.; Le Gall, T.; Montier, T.; Pichon, C.; Malinge, J.-M. Cardiolipin-Based Lipopolyplex Platform for the Delivery of Diverse Nucleic Acids into Gram-Negative Bacteria. Pharmaceuticals 2019, 12, 81.

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