open access

https://hdl.handle.net/2115/79729

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

英語

Spleen

2019-11-10

Elsevier

Journal of controlled release

313

70-79

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.

学術雑誌論文

Accepted Manuscript

Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International

©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/

0168-3659