Enhancement of Gene Silencing Effect and Membrane Permeability by Peptide-Conjugated 27-Nucleotide Small Interfering RNAReportar como inadecuado




Enhancement of Gene Silencing Effect and Membrane Permeability by Peptide-Conjugated 27-Nucleotide Small Interfering RNA - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

1

Faculty of Pharmacy, Yasuda Women’s University, 6-13-1 Yasuhigashi, Asaminami-ku, Hiroshima 731-0153, Japan

2

Division of Genetics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan





*

Author to whom correspondence should be addressed.



Abstract Two different sizes of siRNAs, of which one type was 21-nucleotide nt siRNA containing 2-nt dangling ends and the other type was 27-nt siRNA with blunt ends, were conjugated with a nuclear export signal peptide of HIV-1 Rev at the 5′-sense end. Processing by Dicer enzyme, cell membrane permeability, and RNAi efficiency of the peptide-conjugated siRNAs were examined. Dicer cleaved the peptide-conjugated 27-nt siRNA leading to the release of 21-nt siRNA, whereas the peptide-conjugated 21-nt siRNA was not cleaved. High membrane permeability and cytoplasmic localization was found in the conjugates. Moreover, the peptide-conjugated 27-nt siRNA showed increased potency of RNAi in comparison with the nonmodified 21-nt and 27-nt siRNAs, whereas the peptide-conjugated 21-nt siRNA showed decreased RNAi efficacy. This potent RNAi efficacy is probably owing to acceleration of RISC through recognition by Dicer, as well as to the improvement of cell membrane permeability and intracellular accumulation.

Keywords: peptide conjugates; Dicer-substrate; 27-nt siRNA; potent gene silencing; intracellular delivery peptide conjugates; Dicer-substrate; 27-nt siRNA; potent gene silencing; intracellular delivery





Autor: Takanori Kubo 1,* , Kazuyoshi Yanagihara 2, Yuichiro Sato 1, Yasuhiro Morita 1 and Toshio Seyama 1

Fuente: http://mdpi.com/



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