El-Sayed, Ayman and Masuda, Tomoya and Khalil, Ikramy and Akita, Hidetaka and Harashima, Hideyoshi (2009) Enhanced gene expression by a novel stearylated INF7 peptide derivative through fusion independent endosomal escape. Journal of Controlled Release, In Press, Corrected Proof . - . (In Press)
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Official URL: http://www.sciencedirect.com/science/article/B6T3D...
An octaarginine-modified multifunctional envelope-type nano device (R8-MEND) was previously reported to be an efficient nonviral vector for the delivery of plasmid DNA, in vitro and after topical administration. We report herein on a novel stearylated derivative of the INF7 peptide, a derivative of the N-terminal domain of the HA2 protein of the influenza virus envelope, which enhances the endosomal escape of R8-MEND through a mechanism independent of fusion between the MEND coat and the endosomal membrane. The use of the novel peptide derivative would permit the gene expression of the R8-MEND to be improved, both in vitro and in vivo. R8-MEND modified with stearylated INF7 resulted in gene expression levels that were 77-fold higher than unmodified and 20-fold higher than the free INF7 peptide-modified R8-MEND with no cellular toxicity. Spectral imaging in live cells confirmed that the stearylated INF7 modification did not mediate fusion between liposomes and the endosomal membrane. The inclusion of DOPE to the R8-MEND coat was synergistic with the peptide in improving gene transfection. The intravenous injection of an R8-MEND modified with stearylated INF7 to ICR mice resulted in luciferase expression levels 240-fold higher in liver and 115-fold higher in spleen than that of the R8-MEND.
|Uncontrolled Keywords:||Non-viral vector; Envelope-type nano device; Octaarginine; INF7; Endosomal escape|
|Subjects:||Biomedical Science > Nanomedicine|
|Deposited On:||04 Aug 2009 11:00|
|Last Modified:||04 Aug 2009 11:00|
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