A novel antimicrobial peptide-derived vehicle for oligodeoxynucleotide delivery to inhibit TNF-α expression.
Indolicidin (IL), an antimicrobial peptide, was investigated as a vehicle to promote oligodeoxynucleotides (ODNs) delivery. To increase charge density, IL was dimerized by adding a cysteine to its C or N terminus, which was denoted as ILC or CIL, respectively. In contrast to IL, cytotoxicity of ILC and CIL was significantly reduced because these dimeric peptides were longer than IL, which restricted their insertions to cell membrane. In contrast to ILC, CIL displayed well loading efficiency. These peptides were applied to deliver ODNs against tumor necrosis factor-α (TNF-α) because TNF-α is a pro-inflammatory cytokine which plays an important role in immunological diseases. Although IL/ODN slightly reduced TNF-α expression, the high cytotoxicity restricted its application window. Furthermore, ILC/ODN was incapable of inducing gene silence due to its low encapsulation efficiency and poor endosomal escape. In contrast, CIL exhibited excellent ODN transportation and the internalized CIL/ODN complexes may escape from endosomes. Therefore, TNF-α expression can be specifically reduced by CIL/ODN complexes, and the silence effect was maintained longer than 14 h. This study provides a useful strategy of peptide vehicle design, which may facilitate the delivery of not only ODN but also other oligonucleotides, including siRNA and miRNA, to promote gene silence application.
['Hu|Wei-Wen|WW|', 'Huang|Shih-Chun|SC|', 'Jin|Shiow-Lian Catherine|SC|']
D000818:Animals D023181:Antimicrobial Cationic Peptides D002470:Cell Survival D020868:Gene Silencing D051379:Mice D009838:Oligodeoxyribonucleotides D000067996:RAW 264.7 Cells D014409:Tumor Necrosis Factor-alpha
Oligodeoxynucleotides Indolicidin Tumor necrosis factor-α Gene silence Peptide dimerization