Schistosome Transfection Using A Cationic Polymer

使用阳离子聚合物进行血吸虫转染

基本信息

批准号：
8698583
负责人：
Emmitt Randolph Jolly
金额：
$ 22.81万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8698583
关键词：
Address Adult Affect Affinity Antibodies Antiparasitic Agents Area Biolistics Biological Assay Biology Cathepsins B DNA Data Development Disease Dominant Genetic Conditions Dominant-Negative Mutation Drug Formulations Drug Targeting Electroporation Engineering Gene Expression Gene Expression Regulation Genes Genetic Genome Goals Helminths Human Immunohistochemistry Infection Knock-out Knowledge Laboratories Measures Methodology Methods Modeling Molecular Molecular Genetics Mutation National Institute of Allergy and Infectious Disease New Agents Nucleic Acids Parasites Pathway interactions Pharmaceutical Preparations Plasmids Polyethyleneimine Polymers Praziquantel Process Protein Overexpression Proteins Proteomics Protocols documentation RNA RNA Interference Schistosoma Schistosome Parasite Schistosomiasis Signal Transduction Small Interfering RNA Snails Sporocysts Staging System Techniques Testing Transcript Transfection United States National Institutes of Health Viral base design drug development egg genetic manipulation improved interest knockout gene novel overexpression plasmid DNA programs promoter public health relevance research study tool

项目摘要

DESCRIPTION (provided by applicant): Schistosomiasis is a global disease that infects more than 207 million people worldwide. Treatment for schistosomiasis primarily relies on the drug, praziquantel, which has been in use for more than 30 years. Although praziquantel is available, over 250,000 people die each year from complications associated with schistosome infection, and there are few new anti-schistosome drugs undergoing active development. The schistosome genome has been sequenced, but a major hurdle for schistosome drug development has been the inability to efficiently manipulate schistosome genetically resulting in our limited understanding of schistosome molecular programs. Our long-term goals are to rationally identify potential drug targets for use against schistosomiasis. We plan to progress toward this goal by defining the regulatory programs required for schistosome development and viability. This process can be facilitated with tools that promote our ability to genetically modif and manipulate schistosome parasites. This study provides an alternative and new method for the transfection of nucleic acid in schistosomes to genetically control schistosome signaling systems through DNA overexpression, protein localization, and the utilization and the development of RNA interference strategies. It will simplify and improve current methods for transfection and will have a major impact on schistosome, and parasitic worm molecular genetics in general.

描述（由申请人提供）：血吸虫病是一种全球疾病，在全球范围内感染了超过2.07亿人。血吸虫病的治疗主要取决于已使用已有30多年的药物Praziquantel。尽管可以使用praziquantel，但每年有25万人因与棘突感染相关的并发症而死亡，而且很少有新的抗速溶药物正在积极发展。血吸虫基因组已经进行了测序，但是黑素药物开发的主要障碍是无法有效地操纵棘细胞体遗传学，从而导致我们对血吸虫分子程序的理解有限。我们的长期目标是合理地确定潜在的药物靶标，以抗血吸虫病。我们计划通过定义实体开发和生存能力所需的监管计划来朝着这一目标迈进。可以使用工具来促进此过程，从而促进我们对基因修饰和操纵棘细菌寄生虫的能力。这项研究为通过DNA的过表达，蛋白质定位以及RNA干扰策略的利用和发展提供了一种替代性和新方法，用于通过DNA过表达，蛋白质定位以及利用和开发，以遗传控制核酸的核酸转染。它将简化和改善当前转染的方法，并将一般对棘虫分子遗传学产生重大影响。