G-quadruplex-based CpG oligodeoxynucleotide/DOTAP complex strongly stimulates immunity in CpG motif-specific and loop-length-dependent manners.

Autor: Tu ATT; Research Center for Functional Materials, National Institute for Materials Science, Tsukuba, Japan; Division of Life Science, Hokkaido university, Sapporo, Japan., Hoshi K; Research Center for Functional Materials, National Institute for Materials Science, Tsukuba, Japan., Shobo M; Research Center for Functional Materials, National Institute for Materials Science, Tsukuba, Japan., Yamazaki T; Research Center for Functional Materials, National Institute for Materials Science, Tsukuba, Japan; Division of Life Science, Hokkaido university, Sapporo, Japan. Electronic address: YAMAZAKI.Tomohiko@nims.go.jp.
Jazyk: angličtina
Zdroj: Nanomedicine : nanotechnology, biology, and medicine [Nanomedicine] 2022 Feb; Vol. 40, pp. 102508. Date of Electronic Publication: 2021 Dec 11.
DOI: 10.1016/j.nano.2021.102508
Abstrakt: Guanine-quadruplex (G4) oligodeoxynucleotides (ODNs) that contain unmethylated cytosine-phosphate-guanine motifs (G4 CpG ODN) with phosphodiester backbones are safer than the phosphorothioate (PT)-modified CpG ODNs recently used as vaccine adjuvants. However, cellular uptake and the nuclease stability of G4 CpG ODNs are still insufficient, resulting in lower immunostimulatory activity than PT-modified CpG ODNs. We aimed to enhance the immunostimulatory properties of G4 CpG ODNs by complexing with the cationic liposome 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). The complex acquired nuclease resistance and improved cellular uptake. The immunostimulatory activity of the G4 CpG ODN-DOTAP lipoplexes was enhanced to a level comparable to that of PT-modified ODNs. In addition, the lipoplexes based on unmodified G4 CpG ODNs demonstrated CpG motif-specific immunostimulant activity, although PT-modified ODNs lacking the CpG motif could activate human immune cells. Interestingly, G4 CpG ODN-DOTAP lipoplexes induced interferon-α production in a loop-length dependent manner.
Competing Interests: Declaration of competing interest The authors declare no competing financial interest.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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