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Updated: Aug 10, 2025
Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
Published on: February 1, 2019
Engineered liposomes to deliver nucleic acid mimics in Escherichia coli
Luís Moreira1, Nuno M Guimarães1, Sara Pereira1
1LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
Abstract:
Antisense oligonucleotides (ASOs) composed of nucleic acid mimics (NAMs) monomers are considered as potential novel therapeutic drugs against bacterial infections. However, bacterial envelopes are generally impermeable to naked oligonucleotides. Herein, liposomes loaded with NAMs-modified oligonucleotides (LipoNAMs) were evaluated to deliver ASOs in Escherichia coli. Specifically, we tested several surface modifications that included methoxyPEG conjugated to different lipid anchors or modification of the PEG distal ends with maleimide groups and antibodies. MethoxyPEG coated LipoNAMs showed low delivery efficiency for most bacteria, but maleimide-functionalized PEG LipoNAMs were able to deliver ASOs to nearly half of the bacterial population. Conjugation of antibodies to maleimide-functionalized PEG LipoNAMs increased 1.3-fold the delivery efficiency, enhancing the selectivity towards E. coli and biocompatibility. This work demonstrated for the first time that the coupling of antibodies to PEGylated liposomes can significantly improve the delivery of ASOs in E. coli, which might bring alternative routes for the treatment of bacterial infections in the future.
