Delivery of siRNA mediated by histidine-containing reducible polycations

Research output: Contribution to journalArticle

Standard

Delivery of siRNA mediated by histidine-containing reducible polycations. / Stevenson, M; Ramos-Perez, V; Singh, S; Soliman, M; Preece, Jon; Briggs, SS; Read, Martin; Seymour, LW.

In: Journal of Controlled Release, Vol. 130, No. 1, 01.08.2008, p. 46-56.

Research output: Contribution to journalArticle

Harvard

Stevenson, M, Ramos-Perez, V, Singh, S, Soliman, M, Preece, J, Briggs, SS, Read, M & Seymour, LW 2008, 'Delivery of siRNA mediated by histidine-containing reducible polycations', Journal of Controlled Release, vol. 130, no. 1, pp. 46-56. https://doi.org/10.1016/j.jconrel.2008.05.014

APA

Vancouver

Author

Stevenson, M ; Ramos-Perez, V ; Singh, S ; Soliman, M ; Preece, Jon ; Briggs, SS ; Read, Martin ; Seymour, LW. / Delivery of siRNA mediated by histidine-containing reducible polycations. In: Journal of Controlled Release. 2008 ; Vol. 130, No. 1. pp. 46-56.

Bibtex

@article{7249282cc4e04e1bb5b66655c5e817c0,
title = "Delivery of siRNA mediated by histidine-containing reducible polycations",
abstract = "Histidine containing reducible polycations based on CH6K3H6C monomers (His6 RPCs), are highly effective DNA transfection agents combining pH buffering endosomal escape mechanisms with rapid unpackaging following reduction in the cytoplasm. We examined their ability to mediate siRNA uptake into cells focusing on hepatocyte delivery. Co-delivery of EGFP siRNA with pEGFP plasmid DNA reduced reporter gene expression by 85%. However while DNA transfection efficiency increased with polymer size, with 162 k His6 RPCs proving the most effective, delivery of siRNA alone to EGFP stably expressing cells was only possible using 36-80 k polymers. Analysis of particle sizes showed that 80 k polymers formed more compact siRNA complexes than 162 k polymers. The reducible nature of the polymer was necessary for siRNA activity, since siRNA combined with non-reducible polylysine showed little activity. Incorporation of a targeting peptide from the Plasmodium falciparum circumsporozoite (CS) protein onto His6 RPCs, significantly improved transfection of plasmid DNA and siRNA activity in hepatocytes, but not in most non-liver cells tested. siRNA targeted to the hepatitis B virus surface antigen delivered by CS-His6 RPC, mediated falls in both mRNA and protein expression, suggesting that this delivery system could be developed for potential therapies for viral hepatitis. (C) 2008 Elsevier B.V. All rights reserved.",
keywords = "gene therapy, non-viral delivery, Plasmodium falciparum circumsporozoite, RNAi, hepatitis",
author = "M Stevenson and V Ramos-Perez and S Singh and M Soliman and Jon Preece and SS Briggs and Martin Read and LW Seymour",
year = "2008",
month = aug,
day = "1",
doi = "10.1016/j.jconrel.2008.05.014",
language = "English",
volume = "130",
pages = "46--56",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - Delivery of siRNA mediated by histidine-containing reducible polycations

AU - Stevenson, M

AU - Ramos-Perez, V

AU - Singh, S

AU - Soliman, M

AU - Preece, Jon

AU - Briggs, SS

AU - Read, Martin

AU - Seymour, LW

PY - 2008/8/1

Y1 - 2008/8/1

N2 - Histidine containing reducible polycations based on CH6K3H6C monomers (His6 RPCs), are highly effective DNA transfection agents combining pH buffering endosomal escape mechanisms with rapid unpackaging following reduction in the cytoplasm. We examined their ability to mediate siRNA uptake into cells focusing on hepatocyte delivery. Co-delivery of EGFP siRNA with pEGFP plasmid DNA reduced reporter gene expression by 85%. However while DNA transfection efficiency increased with polymer size, with 162 k His6 RPCs proving the most effective, delivery of siRNA alone to EGFP stably expressing cells was only possible using 36-80 k polymers. Analysis of particle sizes showed that 80 k polymers formed more compact siRNA complexes than 162 k polymers. The reducible nature of the polymer was necessary for siRNA activity, since siRNA combined with non-reducible polylysine showed little activity. Incorporation of a targeting peptide from the Plasmodium falciparum circumsporozoite (CS) protein onto His6 RPCs, significantly improved transfection of plasmid DNA and siRNA activity in hepatocytes, but not in most non-liver cells tested. siRNA targeted to the hepatitis B virus surface antigen delivered by CS-His6 RPC, mediated falls in both mRNA and protein expression, suggesting that this delivery system could be developed for potential therapies for viral hepatitis. (C) 2008 Elsevier B.V. All rights reserved.

AB - Histidine containing reducible polycations based on CH6K3H6C monomers (His6 RPCs), are highly effective DNA transfection agents combining pH buffering endosomal escape mechanisms with rapid unpackaging following reduction in the cytoplasm. We examined their ability to mediate siRNA uptake into cells focusing on hepatocyte delivery. Co-delivery of EGFP siRNA with pEGFP plasmid DNA reduced reporter gene expression by 85%. However while DNA transfection efficiency increased with polymer size, with 162 k His6 RPCs proving the most effective, delivery of siRNA alone to EGFP stably expressing cells was only possible using 36-80 k polymers. Analysis of particle sizes showed that 80 k polymers formed more compact siRNA complexes than 162 k polymers. The reducible nature of the polymer was necessary for siRNA activity, since siRNA combined with non-reducible polylysine showed little activity. Incorporation of a targeting peptide from the Plasmodium falciparum circumsporozoite (CS) protein onto His6 RPCs, significantly improved transfection of plasmid DNA and siRNA activity in hepatocytes, but not in most non-liver cells tested. siRNA targeted to the hepatitis B virus surface antigen delivered by CS-His6 RPC, mediated falls in both mRNA and protein expression, suggesting that this delivery system could be developed for potential therapies for viral hepatitis. (C) 2008 Elsevier B.V. All rights reserved.

KW - gene therapy

KW - non-viral delivery

KW - Plasmodium falciparum circumsporozoite

KW - RNAi

KW - hepatitis

U2 - 10.1016/j.jconrel.2008.05.014

DO - 10.1016/j.jconrel.2008.05.014

M3 - Article

C2 - 18571758

VL - 130

SP - 46

EP - 56

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 1

ER -