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.
|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|