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Engineering Peptide‐Oligonucleotide Nano‐Conjugates via Click Reaction as Self‐Delivery System for Gene Therapy of Inflammatory Arthritis.

Authors :
Wang, Qing
Wang, Wei
Peng, Xiaole
Ge, Gaoran
Li, Wenhao
Zhu, Chen
Chen, Xu
Guo, Shun
Li, Ning
Yang, Huilin
Xu, Yaozeng
Bai, Jiaxiang
Pan, Guoqing
Geng, Dechun
Source :
Advanced Functional Materials. 10/8/2024, Vol. 34 Issue 41, p1-18. 18p.
Publication Year :
2024

Abstract

Intracellular oligonucleotide delivery possesses unparalleled potential for precise regulation of pathogenic gene expression and alteration of cell destiny. However, limited by its feeble resistance against humoral environment, hindered intracellular transportation, and lysosomal phagocytosis, oligonucleotide therapy remains a formidable challenge. The discovery of cationic peptides has provided innovative insights for the effective delivery of oligonucleotides, yet the stable, efficient, and convenient assembly of peptides and oligonucleotides remains an elusive goal, referred to as the "Holy Grail" challenge in the field. Addressing this challenge, it has pioneered the development of a straightforward and highly efficient engineering carrier‐free covalent peptide‐oligonucleotide nano‐conjugates (PONs) through a mild click reaction. Notably, this PONs can realize self‐assemble into nanoparticles under amphiphilic electrostatic interactions, which exhibits significant RNase resistance and surprisingly effective intracellular oligonucleotide delivery as well as lysosomal escape. Based on this strategy, a PONs named CPP‐(DOPA)6‐miRNA‐223 is synthesized, which demonstrates rapid and effective cellular uptake, swift lysosomal escape in macrophage, remarkable accumulation in inflammatory regions and excellent therapeutic effect in an inflammatory arthritis model. Therefore, this work may provide a breakthrough for the clinical application of all oligonucleotide delivery therapies and expanding the applications in gene therapy. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1616301X
Volume :
34
Issue :
41
Database :
Academic Search Index
Journal :
Advanced Functional Materials
Publication Type :
Academic Journal
Accession number :
180150099
Full Text :
https://doi.org/10.1002/adfm.202406503