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

Novel DNA encoded monoclonal antibodies (DMAbs) for control of Antimicrobial Resistant (AMR) Pseudomonas aeruginosa infection

用于控制抗菌素耐药性 (AMR) 铜绿假单胞菌感染的新型 DNA 编码单克隆抗体 (DMAb)

基本信息

批准号：
10459450
负责人：
DAVID B. WEINER
金额：
$ 97.92万
依托单位：
WISTAR INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10459450
关键词：
Acinetobacter baumannii Address Affinity Animal Model Animals Anti-Bacterial Agents Antibiotic Resistance Antibiotics Antigen Receptors Antimicrobial Resistance Bacteria Burn injury Categories Cell Degranulation Centers for Disease Control and Prevention (U.S.)Clinic Cold Chains Communicable Diseases Communication Communities DNA DNA delivery Data Development Directed Molecular Evolution Dose Drug resistance Drug resistant Pseudomonas aeruginosa ESKAPE pathogens Engineering Enterobacter Enterococcus faecium Formulation Genes Goals Half-Life Hospitalization IgG Receptors Immunoglobulin G Infection Infection Control Intervention Klebsiella pneumoniae Lead Length Medical Modeling Modification Monitor Monoclonal Antibodies Mus National Institute of Allergy and Infectious Disease Natural Killer Cells Nature Nosocomial Infections Oryctolagus cuniculus Pharmacologic Substance Phase Population Population Heterogeneity Procedures Production Property Proteins Pseudomonas aeruginosa Pseudomonas aeruginosa infection Public Health Publishing Regimen Resistance Serum Staphylococcus aureus Technology The Wistar Institute Therapeutic Time Translating Translations Work World Health Organization antibiotic resistant infections antigen binding antimicrobial antimicrobial resistant infection antimicrobial resistant pathogen clinical development cost cost effective cytotoxic design in silico in vivo innovation lead optimization lead series microorganism multidrug-resistant Pseudomonas aeruginosa nonhuman primate novel novel strategies novel therapeutics preclinical study prevent priority pathogen research clinical testing respiratory skin wound synthetic construct

项目摘要

Project Summary The control of highly antimicrobial resistant (AMR) infections like multi-drug resistant Pseudomonas aeruginosa is a serious global public health concern. Multi-drug resistant P. aeruginosa are one of the top AMR micro- organisms, presenting a major challenge for infection control. Alternative interventions to traditional antimicrobials are urgently needed. Monoclonal antibodies (mAbs) targeting highly conserved proteins represent an important approach against infectious diseases. MAbs can be delivered immediately prior to hospitalization or a medical procedure to prevent or control infection. However, protein mAb delivery technology is severely limited by high manufacturing costs, slow development and long-term production, and a requirement for several high-dose administrations (mg/kg). These limitations tend to make protein mAb delivery a challenge for general administration and restrict its administration to limited populations. Our team has developed DMAb technology, a transformative approach that addresses these critical issues through encoding mAb genes into an optimized DNA platform that is administered directly in vivo. DMAbs reach protective levels in vivo with direct antimicrobial activity rapidly, can be manufactured simply and quickly, can likely avoid cold chain requirements, and are highly cost-effective compared to protein IgG. In a recent study, we demonstrated that engineered DMAbs can effectively deliver mAb in vivo to control MDR P. aeruginosa infection in mice (Patel, DiGiandomenico et al Nat. Comm. 2017). Our goal is to build on this work, through further enhancement in DMAb technology and to translate this approach into a strategy for control of antibiotic resistant infections. We are proposing to enhance the properties of our well-characterized DMAb lead-series directed against MDR P. aeruginosa and to develop more potent forms with enhanced antigen binding and receptor engagement to control infection. In this proposal, we will perform important studies to support translation of this approach to larger animals and ultimately to move to IND submission.

项目总结