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

Targeted Gene Delivery Systems Treating Lung Diseases

治疗肺部疾病的靶向基因传递系统

基本信息

批准号：
10645109
负责人：
MATTHEW TIRRELL
金额：
$ 79.7万
依托单位：
UNIVERSITY OF CHICAGO
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：
2022-06-15 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10645109
关键词：
2019-nCoV Acute Acute Lung Injury Acute Respiratory Distress Syndrome Alveolar Alveolus Animal Experiments Autopsy Bleomycin Blood Vessels COVID-19 COVID-19 pandemic COVID-19 patient COVID-19/ARDS Cause of Death Cells Chicago Chronic Chronic lung disease Cicatrix Community Medicine Complication Critical Illness Data Disease Encapsulated Endothelium Engineering Fibroblasts Fright Genetic Goals Health Human Impairment Infection Inflammatory Influenza Knowledge Lung Lung diseases Medical Messenger RNA Modification Molecular Molecular Profiling Molecular Target Morbidity - disease rate Mus Patients Peptides Perfusion Pharmacological Treatment Phase Plasmids Platelet-Derived Growth Factor beta Receptor Population Process Protein Disulfide Isomerase Proteins Public Health Publishing Pulmonary Fibrosis Pulmonary Inflammation RNA vaccine Research Reticulum Risk Slice Stimulus TXN gene Testing Therapeutic Therapeutic Effect Tidal Volume Universities Uridine Vascular Cell Adhesion Molecule-1 Vascular Endothelial Cell Viral Viral Physiology Viral Pneumonia Virus Water Work cell type cytokine release syndrome endoplasm endothelial dysfunction fibrotic lung gene delivery system high risk immunogenicity in vivo in vivo evaluation inflammatory lung disease lung injury mortality nanomedicine nanoparticle overexpression pandemic influenza protein expression pulmonary function small hairpin RNA therapeutic effectiveness therapeutic evaluation transcription factor vascular endothelial dysfunction ventilation

项目摘要

Project Summary This R01 proposal outlines a research plan which uses targeted nanomedicine to enhance disease- modifying molecular mechanisms both in the acute injurious phase and in the subsequent chronic fibrotic phase of viral-induced pneumonitis. The overall goal of this proposal is to use nanomedicine to modify specific cellular subtypes during the lung disease process. Acute and chronic lung diseases are major causes of mortality and morbidity in the US. Acute respiratory distress syndrome (ARDS), caused by widespread endothelial barrier disruption and uncontrolled cytokine storm, is the major cause of death in critically ill influenza and COVID-19 patients. Furthermore, pulmonary fibrosis, progressive scarring in injured lung, is a major sequelae of viral pneumonia. Early analyses showed that discharged COVID-19 patients are at high risk for developing pulmonary fibrosis. Currently, there are few pharmacological treatments that directly targets ARDS, and available therapeutic options for pulmonary fibrosis remain suboptimal, underscoring unmet medical needs in a heightened state due to COVID-19 pandemic. Strongly supported by our published and unpublished in vivo results, we believe that targeted nanomedicine approaches have tremendous potential to treat ARDS and pulmonary fibrosis, which will be comprehensively tested in vivo in this application. Aim 1 will test the therapeutic effectiveness of specifically reducing endothelial dysfunction in acute lung injury (influenza or SARS-CoV-2) in mice and perfused human lungs using a VCAM1-targeting, KLF2 mRNA-encapsulated nanoparticles. We anticipate that specific endothelial KLF2 overexpression will reduce acute lung injury. Aim 2 will test the therapeutic effectiveness of specifically targeting lung fibroblasts in chronic pulmonary fibrosis (bleomycin) in mice and human lung slices using PDGFRB-targeting nanoparticles to deliver shRNAs against TXNDC5. We anticipate that specific fibroblast inhibition of TXNDC5 will reduce lung fibrosis.

项目总结

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Sequence-Controlled Secondary Structures and Stimuli Responsiveness of Bioinspired Polyampholytes.

仿生聚两性电解质的序列控制二级结构和刺激响应性。

DOI：
10.1021/acs.biomac.2c00666
发表时间：
2022
期刊：
Biomacromolecules
影响因子：
6.2
作者：
Dinic,Jelena;Schnorenberg,MathewR;Tirrell,MatthewV
通讯作者：
Tirrell,MatthewV

Manipulation of coacervate droplets with an electric field.

DOI：
10.1073/pnas.2203483119
发表时间：
2022-08-09
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
通讯作者：

Scattering evidence of positional charge correlations in polyelectrolyte complexes.

DOI：
10.1073/pnas.2302151120
发表时间：
2023-08-08
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Fang, Yan N.;Rumyantsev, Artem M.;Neitzel, Angelika E.;Liang, Heyi;Heller, William T.;Nealey, Paul F.;Tirrell, Matthew V.;de Pablo, Juan J.
通讯作者：
de Pablo, Juan J.