Mid-Scale RNA Synthesis, Purification and Quality Control System

 描述（由申请人提供）： 基于寡核苷酸的治疗和体内功能基因组学是研究和开发的前沿领域。马萨诸塞州大学医学院教授克雷格·梅洛发现了RNAi，获得了2006年的诺贝尔奖。基于RNAi和反义的药物已被证明具有临床疗效，并被认为将成为一种新的主要治疗方式。在马萨诸塞州大学医学院（UMMS），有多个研究小组的研究已经达到了需要在动物模型和临床前开发中对新型和先进寡核苷酸进行功能分析的阶段。这些类型的研究需要获得中等规模的独特化学修饰的寡核苷酸，这些寡核苷酸的商业可用性有限，并且超出了学术研究人员的范围。共享仪器补助金将使我们能够购买设备，以支持化学修饰RNA的中等规模合成，纯化和质量控制，这将使正在进行和计划的动物模型和临床前研究得到11个NIH赠款和私人基金会的多个赠款的支持。具体而言，我们正在申请资金购买GE AKTA Pilot 10 RNA合成仪、218 Prep HPLC和6530 QTOF LC-MS。获得这种最先进的RNA合成能力将推动我们的研究和翻译计划，并能够开发新的基于RNA的疗法，特别是用于治疗先兆子痫、ALS（肌萎缩侧索硬化）、HSAN（遗传性感觉和自主神经病变）、亨廷顿舞蹈病、IBD（炎性肠病）和其它疾病。

 DESCRIPTION (provided by applicant): Oligonucleotide- based therapeutics and in vivo functional genomics is a cutting-edge area of research and development. The discovery of RNAi by University of Massachusetts Medical School Professor Craig Mello received the Nobel Prize in 2006. RNAi and Antisense-based drugs have proven clinical efficacy and are believed to become a novel major class of therapeutic modalities. At the University of Massachusetts Medical School (UMMS), there are multiple groups whose research has reached the stage at which functional analysis of novel and advanced oligonucleotides in animal models and preclinical development is necessary. These types of studies require access to mid-scale, uniquely chemically modified oligonucleotides that have limited commercial availability and are outside the reach of academic investigators. A Shared Instrumentation Grant will allow us to purchase the equipment to support mid scale synthesis, purification and quality control of chemically modified RNA that will enable ongoing and planned animal models and preclinical studies for research supported by 11 NIH grants and multiple grants from private foundations. Specifically, we are requesting funds to purchase a GE AKTA Pilot 10 RNA synthesizer, 218 Prep HPLC and 6530 QTOF LC- MS. The acquisition of this state-of-the-art RNA synthesis capability will propel our research and translational programs and enable the development of novel RNA-based therapies, specifically for treatment of Preeclampsia, ALS (amyotrophic lateral sclerosis), HSAN (hereditary sensory and autonomic neuropathy), Huntington, IBD (inflammatory bowel disease) and other diseases.