Journal
MOLECULAR THERAPY
Volume 26, Issue 4, Pages 1056-1065Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2018.02.010
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Funding
- National Health and Medical Research Council (NHMRC) of Australia [GNT1079492, GNT1069492]
- Sir Edward Dunlop Medical Research Foundation Project Grant
- National Heart Foundation (NHF) Postdoctoral Fellowships
- NHF Paul Korner Innovation Awards
- NHF Australian Indigenous Scholarship
- German Research Foundation (DFG) Fellowship
- NHMRC Principal Research Fellowship
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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 down-regulate 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 (scFv(mVCAM-1)) and a microRNA-126 mimic (M-126) constituting theranostic microbubbles (Targ(MB)-M-126). Targ(MB)-M-126 downregulates VCAM-1 expression in vitro and in an in vivo acute inflammatory murine model. Most importantly, using Targ(MB)-M-126 and ultra-sound-guided burst delivery of M-126, the development of AAA in an angiotensin-II-induced mouse model can be prevented. Overall, we describe a unique biotechnological theranostic approach with the potential for early diagnosis and long-sought-after medical therapy of AAA.
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