Maternal-effect selfish element as gene drive for Anopheles mosquitoes

母体效应自私元素作为按蚊基因驱动

• 批准号: 7784696
• 负责人: Zhijian Jake Tu
• 金额: $ 40.29万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7784696
• 关键词: Alleles; Anopheles Genus; Antidotes; Asia; Attention; Biochemistry; Bite; Candidate Disease Gene; Characteristics; Chromosomes; Communicable Diseases; Culicidae; DNA Transposable Elements; Development; Diagnosis; Disease; Drosophila genus; Drug Controls; Drug resistance; Elements; Embryo; Embryonic Development; Ensure; Essential Genes; Exposure to; Female; Flour; Frequencies; Future; Gene Expression Profile; Gene Targeting; Generations; Genes; Genetic; Genetic Transcription; Genome; Genomics; Genotype; Homing; Human; Indium; Individual; Inherited; Insecticides; Laboratories; Link; Malaria; Measures; Meiosis; Methods; MicroRNAs; Modeling; Molecular Genetics; Monitor; Mosquito-borne infectious disease; Oocytes; Oogenesis; Outcome; Ovary; Population; Population Replacements; Population Study; Process; Reading; Reagent; Recording of previous events; Refractory; Relative (related person); Reporter Genes; Reporting; Research Design; Resource Development; Resources; Reverse Transcriptase Polymerase Chain Reaction; Running; Sampling; Staging; System; Targeted Toxins; Testing; Time; Titanium; Toxin; Transcript; Transgenes; Transgenic Organisms; Tribolium; Vaccines; Variant; Vertebral column; Virginia; Wolbachia; cDNA Library; design; disorder control; endonuclease; exposed human population; genetic effector; genetic element; genome sequencing; novel strategies; offspring; pathogen; promoter; prototype; public health relevance; tool; vector; vector mosquito

DESCRIPTION (provided by applicant): Anopheline mosquitoes are the primary vectors of malaria, one of the deadliest and most costly diseases in human history. Measures to control malaria are becoming less effective as both insecticide- and drug-resistance increases. It is clear that new approaches are urgently needed. A new strategy to control mosquito-borne diseases proposes to introduce so-called effector genes or refractory genes into the mosquito that will render the mosquitoes ineffective vectors for pathogens. Developing the means to drive effector genes in natural populations is an urgent priority. The long term objective of this study is to develop an efficient and safe gene drive mechanism that will enable genetic strategies for the control of mosquito-borne infectious diseases. Recently, Chen and colleagues (2007) reported the creation of a synthetic genetic element called Medea in Drosophila that successfully drove population replacement in laboratory. The Drosophila Medea element consists of two parts, a maternally expressed toxin in the form of artificial microRNAs that suppress Myd88, an essential gene for early embryonic development, and a zygotic antidote in the form of a variant of Myd88 that lacks the microRNA targets thus insensitive to the toxin. Building on our preliminary results, we will test the hypothesis that a synthetic Medea gene drive system can be developed in Anopheles stephensi. We will 1) determine the transcriptome profiles during oogenesis and early embryogenesis in An. stephensi; 2) select and test components of An. stephensi Medea; and 3) construct a complete An. stephensi Medea element and test for its maternal-effect selfish characteristics and gene drive ability. PUBLIC HEALTH RELEVANCE: Anopheline mosquitoes are the primary vectors of malaria, which is one of the deadliest and most costly infectious diseases in human history. The long term objective of this study is to develop an efficient and safe gene drive mechanism that will enable genetic strategies for the control of mosquito-borne infectious diseases.

描述（由申请人提供）：按蚊是疟疾的主要传播媒介，疟疾是人类历史上最致命和代价最高的疾病之一。随着杀虫剂和药物耐药性的增加，控制疟疾的措施变得越来越无效。显然，迫切需要新的方法。控制蚊媒疾病的新策略提出将所谓的效应基因或耐药基因引入蚊子中，使蚊子成为病原体的无效载体。开发在自然群体中驱动效应基因的方法是当务之急。这项研究的长期目标是开发一种高效、安全的基因驱动机制，使遗传策略能够控制蚊媒传染病。最近，Chen 及其同事（2007）报道了在果蝇中创建了一种名为 Medea 的合成遗传元件，该元件在实验室中成功地推动了种群更替。果蝇 Medea 元件由两部分组成：一种以人工 microRNA 形式表达的毒素，可抑制 Myd88（早期胚胎发育的必需基因）；另一种为 Myd88 变体形式的合子解毒剂，该变体缺乏 microRNA 靶点，因此对毒素不敏感。基于我们的初步结果，我们将测试可以在史蒂芬按蚊中开发合成美狄亚基因驱动系统的假设。我们将 1) 确定 An 卵子发生和早期胚胎发生过程中的转录组谱。斯蒂芬西； 2）选择并测试An的组件。史蒂芬西·美狄亚； 3）构造一个完整的An。斯蒂芬西美狄亚元素并测试其母性效应的自私特征和基因驱动能力。 公共卫生相关性：按蚊是疟疾的主要传播媒介，疟疾是人类历史上最致命、代价最高的传染病之一。这项研究的长期目标是开发一种高效、安全的基因驱动机制，使遗传策略能够控制蚊媒传染病。