Movement of novel therapeutics from R&D to clinical applications requires the capability to produce the quantity and quality of potential therapeutic agents needed to support in vivo, preclinical, and Phase I clinical studies. Most academic investigators engage commercial manufacturers to meet this need;however, academic investigators developing oligonucleotide-based therapies must first navigate two key manufacturing obstacles. The first is the inability of commercial manufacturing organizations to support novel chemistries (nanoparticles, conjugates, etc.) that are developed In academic labs to address delivery and biostability issues associated with oligonucleotide therapies. The second is the cost associated with obtaining high quality, chemically modified oligonucleotides to support animal studies. Even when commercial manufacturing supports needed chemistries, the cost of goods is usually prohibitively expensive for the academic investigator. If investigators obtain commercial product to perform in vivo, preclinical, and Phase I clinical studies, the supporting pharmacokinetic (PK), pharmacodynamic (PD), and biodistribution (BD) analytic platforms for evaluating trace level oligonucleotides in biological tissues and fluids would not be fully realized due to the rapid evolution of the discovery arena. In addition, simple bioanalytical characterization of therapeutic agents, including structural conformation and stability analysis, as well as in-vivo bioavailability, and on-target/off-target binding studies are often difficult to elucidate due to insufficient analytical technologies. Core C, the MSCC, will address these know hurdles, thus facilitating translational research by supporting academic discovery and development in the context of the DTMI-CTHD. Without the MSCC, costs of outsourced aptamer and antidote oligonucleotide manufacturing with subsequent physicochemical sample characterization would account for a significant portion of each investigator's total budget, and would thus be prohibitively expensive. By setting up an on-campus academic manufacturing and bioanalytical Core, cost savings can be utilized instead to better support the proposed research and facilitate additional project aims.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZHL1-CSR-C)
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Duke University
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Fager, A M; Machlus, K R; Ezban, M et al. (2018) Human platelets express endothelial protein C receptor, which can be utilized to enhance localization of factor VIIa activity. J Thromb Haemost 16:1817-1829
Lee, Jaewoo; Lee, Youngju; Xu, Li et al. (2017) Differential Induction of Immunogenic Cell Death and Interferon Expression in Cancer Cells by Structured ssRNAs. Mol Ther 25:1295-1305
Lee, Jaewoo; Jackman, Jennifer G; Kwun, Jean et al. (2017) Nucleic acid scavenging microfiber mesh inhibits trauma-induced inflammation and thrombosis. Biomaterials 120:94-102
Hoffman, Maureane; Monroe, Dougald M (2017) Impact of Non-Vitamin K Antagonist Oral Anticoagulants From a Basic Science Perspective. Arterioscler Thromb Vasc Biol 37:1812-1818
Nimjee, Shahid M; White, Rebekah R; Becker, Richard C et al. (2017) Aptamers as Therapeutics. Annu Rev Pharmacol Toxicol 57:61-79
Lee, Youngju; Urban, Johannes H; Xu, Li et al. (2016) 2'Fluoro Modification Differentially Modulates the Ability of RNAs to Activate Pattern Recognition Receptors. Nucleic Acid Ther 26:173-82
Soule, Erin E; Bompiani, Kristin M; Woodruff, Rebecca S et al. (2016) Targeting Two Coagulation Cascade Proteases with a Bivalent Aptamer Yields a Potent and Antidote-Controllable Anticoagulant. Nucleic Acid Ther 26:1-9
Ganson, Nancy J; Povsic, Thomas J; Sullenger, Bruce A et al. (2016) Pre-existing anti-polyethylene glycol antibody linked to first-exposure allergic reactions to pegnivacogin, a PEGylated RNA aptamer. J Allergy Clin Immunol 137:1610-1613.e7
Woodruff, Rebecca S; Sullenger, Bruce A (2015) Modulation of the Coagulation Cascade Using Aptamers. Arterioscler Thromb Vasc Biol 35:2083-91
Bompiani, Kristin M; Lohrmann, Jens L; Pitoc, George A et al. (2014) Probing the coagulation pathway with aptamers identifies combinations that synergistically inhibit blood clot formation. Chem Biol 21:935-44