Prevention of mosquito-borne illness through manipulation of the CO2 receptor

描述（由申请人提供）：防治蚊媒疾病的一个关键组成部分是预防疾病。目前的驱蚊剂，如氯菊酯和避蚊胺，已被证明过于昂贵，蚊子最终会对它们产生抗药性。在该提案中，Olfactor Laboratories Inc. (OLI)支持开发用于全球商业和住宅的新型空间非杀虫驱蚊剂。加州大学滨江分校（UCR）的Anandasankar Ray博士证明蚊子中高度保守的二氧化碳受体可以被小分子激活或抑制，基于他的工作，OLI已经鉴定出超过80种分子，这些分子已经被FDA批准用作激活或抑制CO2受体的香料和芳香剂，CO2受体是蚊子的主要宿主寻找机制。通过长时间激活或抑制二氧化碳受体，我们将能够提供驱避性，因为蚊子将无法定位人类的二氧化碳排放量。有了这套安全的二氧化碳受体激活剂和抑制剂，我们已经准备好开始在小面积和飞行试验中进行行为测试。除了作为一个长距离的吸引线索，二氧化碳已被证明是敏感的蚊子皮肤气味和使用小面积着陆试验，我们将能够确定的化合物的功效时，皮肤气味的存在。另一项关键的试验将是飞行试验，包括接触前飞行试验和共同接触飞行试验。预暴露试验将有助于确定剂量依赖性和持续时间的功效，而共同暴露飞行试验将确定与CO2直接竞争时的驱避性。具有至少80%排斥性的单个气味或气味混合物将进行第二阶段测试，其中包括大型观察室和半现场试验。通过这项工作，我们将能够开发用于新型、空间、非杀虫驱蚊剂的活性成分，为疾病预防提供重要的新工具。

DESCRIPTION (provided by applicant): A key component to combating mosquito-borne illnesses is prevention from acquiring the disease. Current mosquito repellents, such as Permethrin and DEET, have been shown to be too costly and mosquitoes can eventually develop resistance to them. In this proposal, Olfactor Laboratories Inc. (OLI) supports the development of novel, spatial, non-insecticidal mosquito repellents for commercial and residential use around the world. Based upon the work of Dr. Anandasankar Ray of the University of California, Riverside (UCR), who demonstrated that the highly conserved carbon dioxide receptor in mosquitoes can be activated or inhibited by small molecules, OLI has identified over 80 molecules which have been approved for use by the FDA for use as flavors and fragrances that activate or inhibit the CO2 receptor, the primary host- seeking mechanism for mosquitoes. Through prolonged activation or inhibition of the carbon dioxide receptor, we will be able to provide repellency since mosquitoes will not be able to locate CO2 emissions from humans for a blood meal. With this suite of safe, carbon dioxide receptor activators and inhibitors, we are ready to begin behavioral testing in small area and flight assays. Apart from serving as a long-range attraction cue, CO2 has been shown to sensitize mosquitoes to skin odors and using small-area landing assays, we will be able to determine efficacy of the compounds when skin odor is present. Another key assay will be the flight assays, consisting of pre-exposure and co-exposure flight assays. Pre-exposure assays will help determine dose-dependent and duration efficacy while co-exposure flight assays will determine repellency when in direct competition with CO2. Individual odors or blends of odors with a repellency of at least 80% will proceed to Phase II testing which will include large observation chambers and semi-field trials. Through this work, we will be able to develop active ingredients for use in novel, spatial, non-insecticidal mosquito repellents to provide an important new tool for disease prevention.