Supplement to Promote Diversity and Inclusion, Female Scientist

项目总结/摘要 目前，超过1亿美国人和全世界15亿人患有慢性 痛苦这比癌症、糖尿病和心脏病加起来还要多。电压门控钠 这些通道负责传递疼痛信号。已经鉴定了9个基因， 每一种都具有独特的性质和组织分布模式。基因研究表明 一种人类钠离子通道亚型的遗传性功能丧失突变？什么？小维1.7一个罕见的 遗传性疾病称为先天性疼痛不敏感（CIP）。患有CIP的人不会 能够感觉到疼痛而没有任何明显的继发性改变。因此，选择性抑制？什么？小维1.7 在正常人中可以重现CIP的表型。然而， 人类？什么？V蛋白使开发选择性抑制剂的大多数努力受挫。我们有 开发了一种非永久性的基因疗法，以靶向非成瘾性疼痛（因为它靶向 非阿片途径）、高度特异性（仅靶向感兴趣的基因）和长期持久 （在小鼠的初步测定中约3周）。在第一阶段SBIR期间，我们将1）测试 其他疼痛目标？在体外？，（2）评估新目标？在体内？在小鼠模型中， 炎性和神经性疼痛。此外，我们还将启动小鼠毒理学研究。在 在第一阶段工作结束时，我们将知道我们优化的活性和安全性的范围。 在II期进行IND毒理学研究的候选人。

Project Summary/Abstract Currently more than 100 million Americans and 1.5 billion people worldwide suffer from chronic pain. This is more than cancer, diabetes, and heart disease combined. Voltage-gated sodium channels are responsible for the transmission of pain signals. Nine genes have been identified, each having unique properties and tissue distribution patterns. Genetic studies have correlated a hereditary loss-of-function mutation in one human Na+ channel isoform – ?Na?V?1.7 – with a rare genetic disorder known as Congenital Insensitivity to Pain (CIP). Individuals with CIP are not able to feel pain without any significant secondary alteration. Thus, selective inhibition of ?Na?V?1.7 in normal humans could recapitulate the phenotype of CIP. However, the high homology of human ?Na?V proteins have frustrated most efforts to develop selective inhibitors. We have developed a non-permanent gene therapy to target pain that is non-addictive (because it targets a non-opioid pathway), highly specific (only targeting the gene of interest), and long-term lasting (around 3 weeks in preliminary assays in mice). During this Phase I SBIR, we will 1) test additional pain targets ?in vitro?, and 2) evaluate the new targets ?in vivo ?in mice models of inflammatory and neuropathic pain. In addition, we will initiate our toxicology studies in mice. At the end of this Phase I work, we will know the spectrum of activity and safety of our optimized candidate to perform IND-enabling toxicology studies in Phase II.