Multi-targeted Antisense Oligonucleotide Delivery by a Framework Nucleic Acid for Inhibiting Biofilm Formation and Virul
- PDF / 2,433,307 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 33 Downloads / 229 Views
ARTICLE
Cite as Nano-Micro Lett. (2020) 12:74 Received: 24 December 2019 Accepted: 12 February 2020 © The Author(s) 2020
https://doi.org/10.1007/s40820-020-0409-3
Multi‑targeted Antisense Oligonucleotide Delivery by a Framework Nucleic Acid for Inhibiting Biofilm Formation and Virulence Yuxin Zhang1, Xueping Xie1, Wenjuan Ma1, Yuxi Zhan1, Chenchen Mao1, Xiaoru Shao1, Yunfeng Lin1 * Yuxin Zhang and Xueping Xie contributed equally to this work. * Yunfeng Lin, [email protected] State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, People’s Republic of China
1
HIGHLIGHTS • A framework nucleic acid delivery system was developed through self-assembly, which can deliver antisense oligonucleotides against multiple targets in bacterial cells. • The ASOs-tFNAs (750 nM) was found to simultaneously inhibit the expression of gtfBCD, gbpB, and ftf, and significantly reduce the extracellular polysaccharide synthesis and biofilm thickness.
ABSTRACT Biofilm formation is responsible for
numerous chronic infections and represents a serious health challenge. Bacteria and the extracellular polysaccharides (EPS) cause biofilms to become adherent, toxic, resistant to antibiotics, and ultimately difficult to remove. Inhibition of EPS synthesis can prevent the formation of bacterial biofilms, reduce their robustness, and promote removal. Here, we have developed a framework nucleic acid delivery system with a tetrahedral configuration. It can easily access bacterial cells and functions by delivering antisense oligonucleotides that target specific genes. We designed antisense oligonucleotide sequences with multiple targets based on conserved regions of the VicK protein-binding site. Once delivered to bacterial cells, they significantly decreased EPS synthesis and biofilm thickness. Compared to existing approaches, this system is highly efficacious because it simultaneously reduces the expression of all targeted genes (gtfBCD, gbpB, ftf). We demonstrate a novel nucleic acid-based nanomaterial with multi-targeted inhibition that has great potential for the treatment of chronic infections caused by biofilms. KEYWORDS Biofilm; Framework nucleic acid; Multi-targeting; Antisense oligonucleotide; Delivery system
Vol.:(0123456789)
13
74
Page 2 of 13
1 Introduction Biofilms represent structured bacterial communities attached to an extracellular matrix secreted by the bacteria on the surface of a living or inanimate body [1]. Bacteria are embedded in these extracellular matrices to protect themselves. Biofilms contain various biological macromolecules, such as extracellular polysaccharides (EPS) and nucleic acids. The EPS matrix enhances the adhesion of bacterial cells and promotes surface microbial accumulation and cohesion, condensing dense cell aggregates and resulting in extremely structured and adherent bacterial biofilms [2]. Therefore, bacteria that form biofilms are 500 to 5000 times more resistant to antibiotics t
Data Loading...
