IngentaConnect Significant and prolonged antisense effect of a multifunctional e...

Authors: Nakamura, Yoshio¹; Kogure, Kentaro²; Yamada, Yuma¹; Futaki, Shiroh³; Harashima, Hideyoshi²

Source: Journal of Pharmacy and Pharmacology, Volume 58, Number 4, April 2006 , pp. 431-437(7)

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 anti-luciferase oligodeoxynucleotide (ODN) condensed by three polycations, stearyl octaarginine (STRR8), 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.

Document Type: Research article

DOI: 10.1211/jpp.58.4.0002

Affiliations: 1: Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan 2: Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan; CREST Japan Science and Technology Agency (JST), Japan 3: PRESTO Japan Science and Technology Agency (JST), Japan; Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan

The full text electronic article is available for purchase. You will be able to download the full text electronic article after payment.

$38.34 plus tax Refund Policy

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