Journal article

Dual-Targeted Theranostic Delivery of miRs Arrests Abdominal Aortic Aneurysm Development

Xiaowei Wang, Amy Kate Searle, Jan David Hohmann, Ao Leo Liu, Meike-Kristin Abraham, Jathushan Palasubramaniam, Bock Lim, Yu Yao, Maria Wallert, Eefang Yu, Yung-Chih Chen, Karlheinz Peter

MOLECULAR THERAPY | CELL PRESS | Published : 2018

Abstract

Abdominal aortic aneurysm (AAA) is an often deadly disease without medical, non-invasive treatment options. The upregulation of vascular cell adhesion molecule-1 (VCAM-1) on aortic endothelium provides an early target epitope for a novel biotechnological theranostic approach. MicroRNA-126 was used as a therapeutic agent, based on its capability to downregulate VCAM-1 expression in endothelial cells and thereby reduces leukocyte adhesion and exerts anti-inflammatory effects. Ultrasound microbubbles were chosen as carriers, allowing both molecular imaging as well as targeted therapy of AAA. Microbubbles were coupled with a VCAM-1-targeted single-chain antibody (scFvmVCAM-1) and a microRNA-126 ..

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Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia


Funding Acknowledgements

The study was supported by the National Health and Medical Research Council (NHMRC) of Australia GNT1079492 and GNT1069492 and the Sir Edward Dunlop Medical Research Foundation Project Grant. X.W. and Y.-C.C. are supported by National Heart Foundation (NHF) Postdoctoral Fellowships and the NHF Paul Korner Innovation Awards. A.K.S. was supported by the NHF Australian Indigenous Scholarship. M.W. was supported by a German Research Foundation (DFG) Fellowship. K.P. was supported by a NHMRC Principal Research Fellowship.