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Adv. Healthc. Mater., 24 November 2024 | https://doi.org/10.1002/adhm.202403281
Lipid Nanoparticle-Mediated CRISPR-Cas13a Delivery for the Control of Bacterial Infection
Bookun Kim1, Hwi Won Seo1, Kyuri Lee2, Dongeun Yong3, Yoon Kyung Park4, Yujin Lee1, Solip Lee1, Do-Wan Kim1, Dajeong Kim1, Choong-Min Ryu1,5
1Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141 Republic of Korea
2College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, 52828 Republic of Korea
3Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, 03722 Republic of Korea
4Department of Biomedical Science, Chosun University, Gwangju, 501–759 Republic of Korea
5Department of Pediatrics School of Medicine, University of California at San Diego, La Jolla, CA, 92093 USA
Corresponding Authors: Dajeong Kim, Choong-Min Ryu
1Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141 Republic of Korea
2College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, 52828 Republic of Korea
3Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, 03722 Republic of Korea
4Department of Biomedical Science, Chosun University, Gwangju, 501–759 Republic of Korea
5Department of Pediatrics School of Medicine, University of California at San Diego, La Jolla, CA, 92093 USA
Corresponding Authors: Dajeong Kim, Choong-Min Ryu
Abstract
Lipid nanoparticles (LNPs) can assist in the delivery of nucleic acid inside animal cells, as demonstrated by their use in COVID-19 vaccine development. However, LNPs applicable to bacteria have not been reported. Here, the screening of 511 LNPs containing random combinations of different lipid components identified two LNPs, LNP 496 and LNP 470, that efficiently delivered plasmids into Escherichia coli BW25113. Since Gram-negative bacteria have lipid bilayers, the bacteria are pretreated with LNP-helper that weakens the bacterial membrane. The cationic lipid DOTAP improved delivery of LNP-encapsulated plasmid DNA when present at a molar ratio of 10–25 mol% in the LNP. LNP encapsulation of the Cas13a/gRNA expression vector controlled infection by a clinical Escherichia strain in Galleria mellonela larvae and mouse infection models when used in combination with non-cytotoxic concentrations of polymyxin B, a bacterial membrane disruptor. Together, the results show that LNPs can be useful as a delivery platform for agents that counteract pathogenic bacterial infections.
논문정보
- Research article
- 2024년 11월 (BRIC 등록일 2024-11-26)
- 국내(교신)+국외 연구진
- 생명과학 > 감염생물학
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