MOLECULAR SYNTHESIS AND CHARACTERIZATION CORE (MSCC)

将新疗法从研发转移到临床应用需要有能力生产出支持体内、临床前和I期临床研究所需的潜在治疗剂的数量和质量。大多数学术研究人员聘请商业制造商来满足这一需求；然而，开发基于寡核苷酸疗法的学术研究人员必须首先导航两个关键的制造 障碍。第一个问题是商业制造组织无法支持新的化学物质(纳米粒子、偶联物等)。这些都是在学术实验室开发的，以解决与寡核苷酸疗法相关的递送和生物稳定性问题。第二个是获得高质量的、化学修饰的寡核苷酸以支持动物研究的成本。即使是商业制造 为了支持所需的化学物质，对于学术研究人员来说，商品的成本通常高得令人望而却步。 如果研究人员获得商业产品进行体内、临床前和I期临床研究，由于发现领域的快速发展，用于评估生物组织和液体中痕量寡核苷酸的支持药代动力学(PK)、药效学(PD)和生物分布(BD)分析平台将无法完全实现。此外，治疗剂的简单生物分析表征， 包括结构构象和稳定性分析，以及体内生物利用度，以及靶上/靶外结合研究往往由于分析技术不足而难以阐明。 核心C，即MSCC，将解决这些已知障碍，从而通过支持DTMI-CTHD背景下的学术发现和发展来促进翻译研究。在没有MSCC的情况下，外包适配子和解毒剂寡核苷酸制造后续物理化学样本的成本 定性将占每个调查员总预算的很大一部分，因此费用将高得令人望而却步。通过在校园内建立学术制造和生物分析核心，可以利用节省的成本来更好地支持拟议的研究，并促进额外的项目目标。

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.