2-5A Antisense Targeting of Telomerase RNA

描述(申请人提供)：核糖核蛋白复合体端粒酶 牵涉到了许多不同的 肿瘤的类型。大约80%的人检测到端粒酶活性 肿瘤细胞类型，但在大多数正常细胞中不存在。因此，对 端粒酶活性是治疗多发性硬化症的一种特别有吸引力的手段 癌症的类型。双子座科技公司正在开发一种新型的 用于反义治疗策略的嵌合寡核苷酸。这些 嵌合体由一个标准的反义成分组成，它引导 到互补的RNA序列的化合物，以及激活剂部分， 2？，5？-寡腺苷(2-5A)，用于激活细胞酶， 核糖核酸酶L(核糖核酸酶L)，裂解靶向核糖核酸。初步研究 已经证明了一种针对端粒酶RNA的2-5A反义化合物 降解抑制卵巢癌细胞的生长和致瘤性 在试管中。拟议研究的目标是使这种化合物取得进展。 通过增加其稳定性，对目标Rina的亲和力， 和通过掺入稳定碱基的抗肿瘤活性 修改。如果成功，2-5A抗端粒酶化合物将具有 广泛应用于多种肿瘤类型的治疗。这些研究将 也影响其他正在开发的反义产品通过改进 2-A反义技术的有效性。

DESCRIPTION (provided by applicant): The ribonucleoprotein complex telomerase has been implicated in the establishment and progression of many different types of tumors. Telomerase activity is detected in roughly 80 percent of all tumor cell types, but is absent in most normal cells. Thus, the disruption of telomerase activity is a particularly attractive means for treating multiple types of cancer. Gemini Technologies Inc. is developing a novel class of chimeric oligonucleotides for use in antisense therapeutic strategies. These chimeras are comprised of a standard antisense component, which directs the compound to complementary RNA sequences, and an activator moiety, 2?,5?-oligoadenylate (2-5A) that serve to activate a cellular enzyme, ribonuclease L (RNase L), which cleaves the targeted RNA. Preliminary studies have shown that a 2-5A antisense compound that targets telomerase RNA for degradation inhibits the growth and tumorigenicity of ovarian carcinoma cells in vitro. The goals of the proposed studies are to progress this compound toward commercialization by increasing its stability, affinity for target RINA, and anti-tumor potential through incorporation of stabilizing base modifications. If successful, the 2-5A anti-telomerase compound will have widespread application to the treatment of many tumor types. These studies will also impact other antisense products under development by improving the effectiveness of the 2-A antisense technology.