Hydrodynamic gene delivery of CC chemokine binding Fc fusion proteins to target acute vascular inflammation in vivo.Report as inadecuate




Hydrodynamic gene delivery of CC chemokine binding Fc fusion proteins to target acute vascular inflammation in vivo. - Download this document for free, or read online. Document in PDF available to download.

Reference: McNeill, E, Iqbal, AJ, White, GE et al., (2015). Hydrodynamic gene delivery of CC chemokine binding Fc fusion proteins to target acute vascular inflammation in vivo. Scientific reports, 5, 17404.Citable link to this page:

 

Hydrodynamic gene delivery of CC chemokine binding Fc fusion proteins to target acute vascular inflammation in vivo.

Abstract: Blockade of CC chemokines is an attractive yet under utilized therapeutic strategy. We report the in vivopharmacokinetics of a broad-spectrum vaccinia virus CC chemokine binding protein (35 K) fused to human IgG1 Fc. We demonstrate that the in vivoefficacy of the protein can be interrogated using hydrodynamic gene delivery of a standard mammalian expression plasmid. High plasma levels of the 35 K-Fc protein are maintained for at least 14 days post gene transfer, with the protein still detectable at 5 weeks. We confirm that the protein has biological activity in acute inflammation, causing a significant reduction in monocyte recruitment during zymosan induced peritonitis. The ability of 35 K-Fc to block more complex pathologies is demonstrated using aortic digests to assess angiotensin II mediated leukocyte recruitment to the aorta. Angiotensin II causes upregulation of mCCL2 in the aorta causing the accumulation of CCR2+cells. Peak monocyte recruitment to the aorta occurs within 3 days and this process is CC chemokine dependent, being significantly reduced by hydrodynamic delivery of 35 K-Fc.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Published version Funder: British Heart Foundation   Funder: Wellcome Trust   Notes:This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Bibliographic Details

Publisher: Nature

Publisher Website: http://www.nature.com/

Journal: Scientific reportssee more from them

Publication Website: http://www.nature.com/srep

Issue Date: 2015-01

Article Number:ARTN 17404

pages:17404Identifiers

Urn: uuid:3d874a2a-e1a0-4f2e-b91f-cf1eb61a5afb

Source identifier: 580231

Eissn: 2045-2322

Doi: https://doi.org/10.1038/srep17404

Issn: 2045-2322 Item Description

Type: Journal article;

Language: eng

Version: Published version Tiny URL: pubs:580231

Relationships





Author: McNeill, E - institutionUniversity of Oxford Oxford, MSD, RDM, RDM Cardiovascular Medicine - - - Iqbal, AJ - institutionUniversit

Source: https://ora.ox.ac.uk/objects/uuid:3d874a2a-e1a0-4f2e-b91f-cf1eb61a5afb



DOWNLOAD PDF




Related documents