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Significant and prolonged antisense effect of a multifunctional envelope-type nano device encapsulating antisense oligodeoxynucleotide

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Title: Significant and prolonged antisense effect of a multifunctional envelope-type nano device encapsulating antisense oligodeoxynucleotide
Authors: Nakamura, Yoshio Browse this author
Kogure, Kentaro2 Browse this author →KAKEN DB
Yamada, Yuma Browse this author →KAKEN DB
Futaki, Shiroh Browse this author
Harashima, Hideyoshi Browse this author →KAKEN DB
Authors(alt): 小暮, 健太朗2
Issue Date: Apr-2006
Publisher: Royal Pharmaceutical Society of Great Britain
Journal Title: Journal of Pharmacy and Pharmacology
Volume: 58
Issue: 4
Start Page: 431
End Page: 437
Publisher DOI: 10.1211/jpp.58.4.0002
PMID: 16597360
Abstract: A multifunctional envelope-type nano device (MEND) was developed for use as an efficient non-viral system for the delivery of plasmid DNA (pDNA) using octaarginine (R8) as an internalizing ligand. Three types of R8-MENDs were prepared, co-encapsulating luciferase-encoding pDNA and antiluciferase oligodeoxynucleotide (ODN) condensed by three polycations, stearyl octaarginine (STR-R8), poly-L-lysine (PLL) and protamine, and the antisense effects of the ODN-encapsulated R8-MENDs (ODN-MEND) were analysed in-vitro. The ODN-MEND packaged using protamine as a condenser showed a 90% antisense effect 16 h after the transfection, and a persistent antisense effect of over 75% for up to 48 h, which was much more effective than that of LipofectAmine2000. On the other hand, the ODN-MENDs prepared using PLL and STR-R8 as condensers did not show any significant inhibition of luciferase activity. Although there was no specific relation between the physicochemical characteristics of the ODN-MENDs and their antisense effect, the pattern of the antisense effect among the ODN-MENDs was similar to that of the silencing effect of R8-MEND encapsulating plasmid DNA encoding siRNA. These results suggest that R8-MENDs are able to deliver encapsulated DNA to the cytosol as well as to the nucleus, and that protamine can also function as an efficient decondenser, not only in the nucleus but also in the cytosol. In conclusion, we successfully developed an ODN-MEND with a high antisense effect using protamine as a DNA condensing as well as a decondensing agent.
Type: article
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: 小暮 健太朗

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