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Delivery of Cell-Specific Aptamers to the Arterial Wall with an Occlusion Perfusion Catheter
Journal article   Open access   Peer reviewed

Delivery of Cell-Specific Aptamers to the Arterial Wall with an Occlusion Perfusion Catheter

Ofonime Udofot, Li-Hsien Lin, William H. Thiel, Megan Erwin, Emily Turner, Francis J. Miller, Paloma H. Giangrande and Saami K. Yazdani
Molecular therapy. Nucleic acids, Vol.16, pp.360-366
06/07/2019
DOI: 10.1016/j.omtn.2019.03.005
PMCID: PMC6462795
PMID: 30986697
url
https://doi.org/10.1016/j.omtn.2019.03.005View
Published (Version of record) Open Access

Abstract

Current strategies to prevent restenosis following endovascular treatment include the local delivery of anti-proliferative agents to inhibit vascular smooth muscle cell (VSMC) proliferation and migration. These agents, not specific to VSMCs, are deposited on the luminal surface and therefore target endothelial cells and delay vascular healing. Cell-targeted therapies, (e.g., RNA aptamers), can potentially overcome these safety concerns by specifically binding to VSMC and inhibiting proliferation and migration. The purpose of this study was to therefore demonstrate the ability of a perfusion catheter to deliver cell-specific RNA aptamer inhibitors directly to the vessel wall. RNA aptamers specific to VSMCs were developed using an in vitro cell-based systematic evolution of ligand by exponential enrichment selection process. Two aptamers (Apt01 and Apt14) were evaluated ex vivo using harvested pig arteries in a pulsatile flow bioreactor. Local drug delivery of the aptamers into the medial wall was accomplished using a novel perfusion catheter. We demonstrated the feasibility to deliver aptamer-based drugs directly to the medial layer of an artery using a perfusion catheter. Such cell-specific targeted therapeutic drugs provide a potentially safer and more effective treatment option for patients with vascular disease.
Life Sciences & Biomedicine Medicine, Research & Experimental Research & Experimental Medicine Science & Technology

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