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Spleen selective enhancement of transfection activities of plasmid DNA driven by octaarginine and an ionizable lipid and its implications for cancer immunization

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Title: Spleen selective enhancement of transfection activities of plasmid DNA driven by octaarginine and an ionizable lipid and its implications for cancer immunization
Authors: Kimura, Seigo Browse this author
Khalil, Ikramy A. Browse this author
Elewa, Yaser H. A. Browse this author
Harashima, Hideyoshi Browse this author →KAKEN DB
Keywords: Gene delivery
pDNA
YSK05
R8
Spleen
Issue Date: 10-Nov-2019
Publisher: Elsevier
Journal Title: Journal of controlled release
Volume: 313
Start Page: 70
End Page: 79
Publisher DOI: 10.1016/j.jconrel.2019.09.009
Abstract: Efficiently delivering plasmid DNA (pDNA) to the spleen is particularly significant for DNA immunization. However, increasing the efficiency of gene expression in spleen cells for achieving a therapeutic effect remains a serious challenge. An ideal spleen-targeted system should avoid liver uptake and should efficiently transfect specific functional spleen cells. Here, we report on pDNA nanocarriers with enhanced transfection in spleen cells driven by synergism between an octaarginine (R8) peptide and YSK05; a pH-responsive ionizable lipid. A double-coating design is essential for enhancing spleen selective transfection which is significantly affected by the total amount of lipid and the composition of the outer coat. The optimized R8/YSK system shows a high gene expression in the spleen with a high spleen/liver ratio and a surprising ability to target spleen B cells. Compared to other organs, the high spleen activity cannot be explained based on the amount of pDNA delivered to each organ, indicating that the system is extremely efficient in transfecting spleen cells. The system can be used in cancer immunization where a strong anti-tumor effect was observed in mice immunized with the R8/YSK system encapsulating antigen-encoding pDNA. The R8/YSK system holds great promise for future applications in the field of DNA vaccination.
Rights: ©2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
https://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article (author version)
URI: http://hdl.handle.net/2115/79729
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 原島 秀吉

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