权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

RNA encoded nanobody-based immunotherapeutics targeting essential, host-interactive schistosome ectoenzymes

RNA 编码的基于纳米抗体的免疫疗法，靶向与宿主相互作用的重要血吸虫胞外酶

基本信息

批准号：
10571150
负责人：
Charles Bix Shoemaker
金额：
$ 24.75万
依托单位：
TUFTS UNIVERSITY BOSTON
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-12-01 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10571150
关键词：
Acetylcholinesterase Ache Adolescent Affinity Alpaca Binding Biochemical Chinese Hamster Ovary Cell Chronic Clinical Trials Country Data Development Disease Drug Kinetics Drug usage Ensure Enzymes Family Fc domain Genetic Transcription Goals Hand Helminths Human Immunize Immunotherapeutic agent In Vitro Infection Infection Control Infection prevention Intervention Laboratory Study Libraries Life Link Longevity Lymphocyte Messenger RNA Methods Molecular Molecular Target Mus Parasites Persons Phage Display Pharmaceutical Preparations Platyhelminths Praziquantel Praziquantel resistance Proteins Publishing RNA RNA Interference Reagent Recombinants Schistosoma Schistosoma mansoni Schistosomatidae Schistosomiasis Series Serum Surface Technology Testing Therapeutic Therapeutic Agents Therapeutic Intervention Tropical Disease Vaccines World Health Organization bone carbonate dehydratase dimer immunogenicity improved in vivo innovation nanobodies novel novel therapeutics phosphoric diester hydrolase prevent pyrophosphatase response success targeted treatment therapeutic RNA tool

项目摘要

Schistosomes are parasitic flatworms that cause a chronic, debilitating disease afflicting >200 million people in >70 countries. Since there are limited anti-schistosome drugs available and since these is no vaccine to prevent infection, we aim here to generate and test nanobody-based immunotherapeutics targeting essential surface-exposed parasite proteins as a novel intervention to control schistosomiasis. Nanobodies (camelid single- domain antibodies or VHHs) are small, versatile binding agents that can be multimerized for enhanced activities and delivered effectively by formulated mRNA. We have identified and characterized three S. mansoni tegumental ectoenzymes (SmNPP5, SmT-AChE, SmCA) that represent novel molecular targets for intervention to treat schistosomiasis. Each of the three enzymes is exposed at the host parasite interface and each is essential for the parasite to infect its vertebrate host. We aim to generate nanobodies that inhibit the function of these three target enzymes (each enzyme has been purified in functional form in CHO-S cells). The small size, stability to heat and pH extremes, low immunogenicity, and facility to express as multimers with enhanced activities, makes VHHs preferred therapeutic agents. We exploit advances in RNA therapeutics as our strategy to efficiently and economically deliver sustained levels of serum VHH-based therapeutics. Our overall goal is to generate a simple, practical, and potent anti-schistosome therapeutic that curtails disease at all stages of infection. In sum, we have identified new, well characterized, accessible and rational targets for anti-schistosome intervention, and we incorporate an innovative, novel, cutting-edge approach to control schistosomiasis. We have assembled a strong team and have on-hand all reagents and tools necessary to ensure the success of this project. Our data will act as a proof of principle supporting an approach that, in the longer term, could form the basis of a new therapeutic for human schistosomiasis, as well as for other debilitating helminth diseases.

血吸虫是一种寄生的扁虫，它会导致一种慢性的、使人衰弱的疾病