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: 7450809
• 负责人: David A O'Brochta
• 金额: $ 31.83万
• 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/7450809
• 关键词: Address; Africa; Animals; Anopheles Genus; Anopheles gambiae; Chromosomes; Class; 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; Numbers; Parasites; Patients; Pattern; Phenotype; Plasmodium; Population; Population Replacements; Purpose; Range; 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）：昆虫传播的疾病，如疟疾，可以通过多种方式控制，从治疗病人到消除传播病原体或寄生虫的昆虫。本文所述的工作将促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。以昆虫遗传学为基础的控制非洲疟疾等疾病的战略正在实验室中发展，并取得了一些成功。利用转基因昆虫技术，已培育出表达多种效应基因的按蚊，这些效应基因可减少或消除这些昆虫支持疟原虫发展的能力。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，为了使实验室创造的有效基因型在控制自然环境中的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，尽管存在一些备选技术。第二类转座因子根据其自然史被认为是基因传播因子。是否有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的转基因仍未得到检验。为了控制疾病传播的目的，在探索操纵媒介能力的可行性方面，这一主要缺陷将在这里提出的工作中得到解决。在An中引入了条件自治的Hermes、Minos、Mos1和piggyBac元素之后。冈比亚将对其重新动员、复制和传播潜力进行定量评估。具体目的是1)评估Hermes， Minos， Mos1和piggyBac在An中的再动员潜力。(2)确定了安安省Hermes， Minos， Mos1和piggyBac的再动员模式。3)评估Hermes， Minos， Mos1和piggyBac在An的繁殖潜力。4)评估Hermes， Minos， Mos1和piggyBac在An的传播潜力。冈比亚按蚊。在本项目结束时，这些转座因素对发展人口替代技术作出贡献的相对希望。冈比亚将为人所知。该项目涉及使用动物，但不涉及人类受试者。