NOVEL CHEMICAL NUCLEASE FOR ANTISENSE THERAPY

反义技术为治疗癌症提供了巨大的希望。 广泛的疾病，包括癌症，传染病和 显性遗传病 尽管这个项目前景广阔 在这方面，几乎没有明显的成功。 为了反- 感觉治疗到达床边必须在几个方面取得进展 包括改进的多核苷酸转移的区域（例如脂质体， 阳离子脂质）和增加的破坏或抑制的 靶向的有义序列。 本提案中的工作将涉及 后一个领域，通过开发一种新的方法来摧毁目标 使用新颖的和创新的化学核酸酶的核酸。 的 先前开发的化学核酸酶不能用于哺乳动物 细胞，因为它们是有毒的，需要强还原剂， 在活细胞中可用。 利用我们复杂而广泛的 了解氧化还原活性化合物的作用机制，我们有 设计了几种高度特异性的核酸酶分子 在活细胞中有活性， 在活细胞中具有活性的高度特异性核酸酶， 有利的性质。 它们毒性低，可以回收利用， 以催化方式切割核酸并利用还原 对哺乳动物细胞来说是丰富的和内源性的试剂。 的 开发这类试剂的实际结果将是一个新的 具有增强的针对广泛的 疾病 商业应用前景：反义基因的新方法 治疗将通过以下方式商业化：1）将技术许可用于 癌症基因疗法的制药公司，2）许可 传染病治疗技术，3）许可 治疗显性遗传疾病的技术，4）出售 以工具包的形式向生物医学研究人员提供技术。

Anti-sense technologies hold tremendous promise for the treatment of a wide range of disease that include cancer, infectious diseases and dominant genetic disorders. Despite the tremendous promise of this approach, there have been few clear successes. In order for anti- sense therapy to reach the bedside there has to be progress in several areas that include improved polynucleotide transfer (e.g. liposomes, catinoic lipids) and increased destruction or inhibition of the targeted sense sequence. The work within this proposal will address the latter area by developing a new method for destroying the targeted nucleic acid using a novel and innovative chemical nuclease. The previously-developed chemical nucleases cannot be used in mammalian cells since they are toxic and require strong reducing agents not available in living cells. Using our intricate and extensive knowledge of mechanisms of action of redox active compounds, we have designed several molecules that should be highly-specific nucleases active in living cells and with several molecules that should be highly-specific nucleases active in living cells and with several advantageous properties. They have low toxicity, can be recycled so as to cut nucleic acids in a catalytic fashion and utilize reducing agents that are plentiful and endogenous to mammalian cells. The practical outcome of developing such class of reagents will be a new family of drugs with enhanced efficacy against a wide spectrum of diseases. PROPOSED COMMERCIAL APPLICATION: The new method of antisense gene therapy will be commercialized by: 1) licensing the technology for cancer gene therapies to pharmaceutical companies, 2) licensing the technology for therapy against infectious diseases, 3) licensing the technology for therapy against dominant genetic disorders, 4) sell the technology in the form of kits to biomedical researchers.