Yolk protein-mediated germline delivery in vector snails

卵黄蛋白介导的媒介蜗牛种系传递

基本信息

批准号：
10214026
负责人：
SI-MING ZHANG
金额：
$ 22.11万
依托单位：
UNIVERSITY OF NEW MEXICO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10214026
关键词：
Address Anatomy Animals Applied Research Basic Science Binding Biology Biomphalaria Castration Cells Characteristics Cleaved cell Clustered Regularly Interspaced Short Palindromic Repeats Complex Development Egg Yolk Proteins Embryo Endosomes Ensure Ferritin Fluorescence Fluorescence Microscopy Fresh Water Generations Genes Genetic Genetic Materials Genetic Techniques Genome Germ Cells Gonadal structure Guide RNA Hemolymph Heritability Injections Interruption Intervention Iron Knock-out Lead Ligand Binding Ligands Mediating Membrane Modeling Modification Oocytes Oviparity Parasites Parasitic Diseases Peptides Play Process Proteins Reagent Recombinant Proteins Reproductive system Ribonucleoproteins Role Schistosomiasis Snails Technology Testing Tissues Transgenic Organisms Vector-transmitted infectious disease Vitellogenesis Vitellogenins base disease transmission egg genetic approach genetic manipulation genome editing innovation interest knockout gene neglected tropical diseases novel programs public health relevance receptor receptor binding receptor mediated endocytosis reproductive success transmission process vector vector control

项目摘要

SUMMARY Genetics-based vector control holds great promise in combating vector transmitted diseases. Such a promising strategy, however, has not yet been tested in any vector snail control program of schistosomiasis, one of the world’s most devastating parasitic diseases. The key reason is the lack of a germline delivery technology for delivering genetic materials into gametes or embryos. The inability to deliver genetic materials into snail germline cells is due to the complex anatomical structure of its gametes, the exceedingly small size of its eggs, and its unusual reproductive system, which preclude the application of all existing, well-developed genetic delivery technologies. To circumvent these limitations, we propose an innovative approach that exploits snail yolk proteins as vehicles for shuttling genetic materials into growing oocytes via the natural process of receptor- mediated endocytosis during vitellogenesis. Two types of the most promising snail yolk proteins, yolk ferritin and vitellogenin, both found present in the genome of the schistosomiasis vector snail Biomphalaria glabrata, will be investigated. We will first identify a highly efficient oocyte receptor-binding ligand from snail yolk ferritin or vitellogenin (Aim1) and then test the identified ligand in delivering clustered regularly interspaced short palindromic repeats (CRISPR) cargo into the oocytes for germline modification (Aim 2). This study will open an exciting door for all genetic manipulation studies for basic and applied research of schistosomiasis.

概括基于遗传学的媒介控制在打击媒介传播疾病方面具有巨大的希望。这样的诺言然而，尚未在任何矢量蜗牛控制程序的血吸虫病中测试过策略，这是其中之一世界上最毁灭性的寄生疾病。关键原因是缺乏用于的种系输送技术将遗传材料输送到游戏或胚胎中。无法将遗传材料输送到蜗牛种系细胞是由于其游戏的复杂解剖结构，其卵的大小较小，及其不寻常的生殖系统，它排除了所有现有的，发达的通用的应用交付技术。为了规避这些限制，我们提出了一种创新的方法来利用蜗牛蛋黄蛋白作为将遗传材料用自然的受体过程的车辆将卵黄发生过程中介导的内吞作用。两种最有前途的蜗牛蛋黄蛋白，蛋黄铁蛋白植物素和植物生成蛋白都存在于血吸虫病矢量蜗牛生物掌labrata的基因组中，将被调查。我们将首先从蜗牛蛋黄铁蛋白中确定高效的卵母细胞受体结合配体或卵黄蛋白（AIM1），然后测试已识别的配体在散布定期插入的短短短短中 alindromic重复（CRISPR）货物进入卵母细胞进行种系修饰（AIM 2）。这项研究将打开对于所有基础研究和应用研究的基础研究研究的令人兴奋的门。