2-5A ANTISENSE INHIBITION OF RESPIRATORY SYNCTIAL VIRUS

描述(摘自申请者摘要)：呼吸道合胞病毒 呼吸道合胞病毒(RSV)是婴幼儿下呼吸道疾病的主要原因 儿童和老年人，特别是那些被收容的人。它是 儿童病毒性毛细支气管炎和肺炎的最常见原因，以及 在冬季的几个月里，疫情经常达到流行的程度， 每年大约有9万人住院，4500人死亡。 双子座科技公司正在开发新型反义嵌合体，用于 呼吸道合胞病毒感染的治疗。这些嵌合体是由一种反义 成分与靶向病毒RNA基因组结合，而2-5A部分 嵌合体能吸引并激活核糖核酸酶L，这是一种能切割 相关的基因组RNA链。在第一阶段的研究中，我们成功地 第二代抗呼吸道合胞病毒嵌合体的合成和检测 在培养细胞和灵长类动物中的抗病毒活性。在这里，我们建议进行 这种化合物通过更明确的动物研究，利用气雾剂 给药以模拟该化合物的临床应用。此外，我们 提出以药物化学为基础的研究，旨在改进嵌合体合成， 以及初步的毒理学研究。 建议的商业应用：不可用

DESCRIPTION (Adapted from Applicant's Abstract): Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in infants, young children and the elderly, particularly those that are institutionalized. It is the most common cause of viral bronchiolitis and pneumonia in children, and outbreaks frequently reach epidemic proportions during the winter months, accounting for roughly 90,000 hospitalizations and 4,500 deaths per year. Gemini Technologies, Inc. is developing novel antisense chimeras for use in the treatment of RSV infections. These chimeras are comprised of an antisense component to the targeted viral RNA genome, while the 2-5A portion of the chimera attracts and activates RNase L, an endoribonuclease that can cleave the associated genomic RNA strand. In the phase I studies, we succeeded in synthesizing and testing a second generation anti-RSV chimera that had potent antiviral activity in cultured cells and in primates. Here we propose to carry this compound through more definitive animal studies, utilizing aerosol delivery to mimic the clinical application of this compound. In addition, we propose medicinal chemistry-based studies aimed at improving chimera synthesis, and preliminary toxicology studies. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE