Gene drive potential of transposable elements in Anopheles gambiae.

描述(申请人提供)：疟疾等昆虫传播的疾病可以通过各种方式得到控制，从治疗病人到消灭传播病原体或寄生虫的昆虫。这里所述的工作将推动评估应用某些昆虫生物技术方法控制疟疾传播的可行性。目前正在开发以昆虫遗传学为基础的控制非洲疟疾等疾病的策略，并在实验室取得了一些成功。利用转基因昆虫技术，已经创造出了表达各种效应基因的按蚊，这些基因降低或消除了这些昆虫支持疟原虫发育的能力。虽然到目前为止生产的昆虫还没有最优的表型，但它们已经证明，利用现有的昆虫基因工程技术，可以破坏疟原虫在按蚊中的发育和传播。然而，为了使有效的实验室创造的基因类型在控制自然环境中的疟疾传播方面具有任何实际用途，必须将它们引入目标物种的自然种群并通过其传播。实现这一目标的技术尚未确定，尽管存在一些候选者。根据其自然历史，第二类转座元件被认为是基因传播剂。现有的昆虫基因载体是否能在冈比亚按蚊种群中传播抗疟原虫转基因仍未得到测试。在为控制疾病传播的目的而操纵病媒能力这一想法的可行性的努力中，这一主要缺陷将在这里提出的工作中得到解决。在将条件自治的Hermes、Minos、Mos1和PiggyBac元素引入An.冈比亚的再动员、复制和传播潜力将得到定量评估。具体目的是：1)评估Hermes、Minos、Mos1和PiggyBac在AN中的再动员潜力。冈比亚亚纲，2)确定了Hermes、Minos、Mos1和PiggyBac在An中的再动员模式。冈比亚，3)评估Hermes、Minos、Mos1和PiggyBac在冈比亚的复制潜力。冈比亚亚科，4)评估Hermes、Minos、Mos1和PiggyBac在冈比亚的传播潜力。冈比亚亚目。在本项目结束时，这些转座元件中的每一个相对承诺为AN的种群替换技术的发展做出贡献。冈比亚亚纲将为人所知。这个项目涉及动物的使用，但不涉及人类科目。

DESCRIPTION (provided by applicant): Insect-born diseases such as malaria can be controlled in a variety of ways ranging from the treatment of sick patients to eliminating the insects that transmit the pathogens or parasites. The work described here will advance efforts to evaluate the feasibility of applying certain insect biotechnological approaches to the control of malaria transmission. Insect genetics-based strategies for controlling diseases such as malaria in Africa are being developed with some success in the laboratory. Using transgenic insect technologies Anopheles mosquitoes have been created that express a variety of effector-genes that reduce or eliminate the capacity of these insects to support Plasmodium development. While the insects produced to date have not had optimal phenotypes they have served to demonstrate that Plasmodium development and transmission in Anopheles mosquitoes can be disrupted using existing insect genetic engineering technologies. However, in order for effective laboratory-created genotypes to be of any practical use in controlling malaria transmission in natural environments they will have to be introduced into and spread through natural populations of the target species. Technologies for accomplishing this objective have yet to be identified although a number of candidates exist. Class II transposable elements have been suggested as gene spreading agents based on their natural history. Whether any of the existing insect gene vectors could serve to spread anti-Plasmodium transgenes through populations of Anopheles gambiae remains untested. This major deficiency in the efforts to explore the feasibility of the idea of manipulating vector competence for the purposes of disease transmission control will be addressed in the work proposed here. Following the introduction of conditionally autonomous Hermes, Minos, Mos1 and piggyBac elements into An. gambiae their remobilization, replication and spreading potential will be quantitatively assessed. The specific aims are to 1) assess the remobilization potential of Hermes, Minos, Mos1 and piggyBac in An. gambiae, 2) determine the patterns of remobilization of Hermes, Minos, Mos1 and piggyBac in An. gambiae, 3) assess the replicative potential of Hermes, Minos, Mos1 and piggyBac in An. gambiae, 4) assess the spreading potential of Hermes, Minos, Mos1 and piggyBac in An. gambiae. At the end of this project the relative promise of each of these transposable elements to contribute to the development of population replacement technology for An. gambiae will be known. This project involves the use of Animals but does not involve Human Subjects.