Gene drive potential of transposable elements in Anopheles gambiae.

冈比亚按蚊转座元件的基因驱动潜力。

• 批准号: 7130828
• 负责人: David A O'Brochta
• 金额: $ 33.41万
• 依托单位: UNIVERSITY OF MD BIOTECHNOLOGY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7130828
• 关键词: Anopheles; Plasmodium; genes; genetics; genotype; malaria; motivation; phenotype; transposon /insertion element

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.

描述（由申请人提供）：虫媒疾病，如疟疾，可以通过多种方式控制，从治疗病人到消灭传播病原体或寄生虫的昆虫。本文所述的工作将推动评估将某些昆虫生物技术方法应用于控制疟疾传播的可行性的努力。目前正在制定以昆虫遗传学为基础的控制非洲疟疾等疾病的战略，并在实验室取得了一些成功。利用转基因昆虫技术，已经创造了按蚊，它们表达了各种效应基因，这些基因降低或消除了这些昆虫支持疟原虫发育的能力。虽然迄今为止产生的昆虫还没有最佳的表型，但它们已经证明，可以使用现有的昆虫基因工程技术破坏按蚊中的疟原虫发育和传播。然而，为了使有效的实验室创造的基因型在自然环境中控制疟疾传播方面具有任何实际用途，它们必须被引入目标物种的自然种群并通过它们传播。实现这一目标的技术尚未确定，尽管存在一些候选技术。II类转座因子基于其自然历史被认为是基因传播因子。是否任何现有的昆虫基因载体可以通过冈比亚按蚊种群传播抗疟原虫转基因仍然未经测试。在探索操纵媒介能力以控制疾病传播的想法的可行性的努力中，这一主要缺陷将在本文提出的工作中得到解决。在将条件自治的爱马仕、Minos、Mos 1和piggyBac元素引入An.冈比亚将对其重新动员、复制和扩散的潜力进行定量评估。具体目标是：1）评估爱马仕、米诺斯、莫斯1和piggyBac在An的再动员潜力。gambiae; 2）确定了爱马仕、Minos、Mos 1和piggyBac在冈比亚按蚊体内的再活动模式。（3）评估爱马仕、Minos、Mos 1和piggyBac在冈比亚按蚊中的复制潜力。评估爱马仕、米诺斯、莫斯1和piggyBac在冈比亚按蚊体内的传播潜力。冈比亚。在这个项目的最后，这些转座因子中的每一个的相对承诺，以促进人口替代技术的发展，为一个。冈比亚将是众所周知的。该项目涉及使用动物，但不涉及人类受试者。