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: 7640580
• 负责人: David A O'Brochta
• 金额: $ 11.8万
• 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 2010-03-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7640580
• 关键词: Address; Africa; Animals; Anopheles Genus; Anopheles gambiae; Chromosomes; Competence; Culicidae; DNA Transposable Elements; Development; Disease; Elements; Engineering; Environment; Genes; Genetic; Genetic Engineering; Genotype; Indium; Insect Genes; Insect Vectors; Insecta; Knowledge; Laboratories; Malaria; Methods; Natural History; Parasites; Patients; Pattern; Phenotype; Plasmodium; Population; Population Replacements; Refractory; Relative (related person); Research Personnel; Target Populations; Technology; Testing; Transgenes; Transgenic Organisms; Vector-transmitted infectious disease; Work; base; disease transmission; disorder control; human subject; insect genetics; pathogen; success; transmission process; vector

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）：疟疾等昆虫传播的疾病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。这里描述的工作将推进评估应用某些昆虫生物技术方法控制疟疾传播的可行性的努力。非洲正在开发基于昆虫遗传学的控制疟疾等疾病的策略，并在实验室取得了一些成功。利用转基因昆虫技术，按蚊被创造出来，它们表达多种效应基因，从而减少或消除这些昆虫支持疟原虫发育的能力。虽然迄今为止生产的昆虫尚未具有最佳表型，但它们已证明可以使用现有的昆虫基因工程技术来破坏按蚊中疟原虫的发育和传播。然而，为了使实验室创建的有效基因型能够实际用于控制自然环境中的疟疾传播，必须将它们引入目标物种的自然种群并通过其传播。尽管存在许多候选技术，但实现这一目标的技术尚未确定。根据其自然历史，II类转座元件被建议作为基因传播剂。现有的昆虫基因载体是否可以用于在冈比亚按蚊种群中传播抗疟原虫转基因，仍有待测试。探索为了控制疾病传播而操纵媒介能力的想法的可行性的努力中的这一主要缺陷将在本文提出的工作中得到解决。继将条件自治的 Hermes、Minos、Mos1 和 PiggyBac 元素引入 An.冈比亚 将对其再动员、复制和传播潜力进行定量评估。具体目标是 1) 评估 Hermes、Minos、Mos1 和 PiggyBac 在 An 中的再动员潜力。冈比亚，2) 确定 An 中 Hermes、Minos、Mos1 和 PiggyBac 的再动员模式。冈比亚，3) 评估 An 中 Hermes、Minos、Mos1 和 PiggyBac 的复制潜力。冈比亚，4) 评估 Hermes、Minos、Mos1 和 PiggyBac 在 An 中的传播潜力。冈比亚。在该项目结束时，这些转座因子中的每一个都有望为安族人口替代技术的发展做出贡献。冈比亚将会为人所知。该项目涉及动物的使用，但不涉及人类受试者。