Phage-inspired nanoparticles with genetically tunable target-specificity

具有基因可调靶点特异性的噬菌体纳米颗粒

基本信息

批准号：
7942938
负责人：
Chuanbin Mao
金额：
$ 40.47万
依托单位：
UNIVERSITY OF OKLAHOMA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7942938
关键词：
Affinity Animals Anterior Arteries Atherosclerosis Automobile Driving Bacteriophages Binding Biological Biomimetics Blood Vessels Blood capillaries Brain C-terminal Capsid Proteins Cardiac Myocytes Cell membrane Cells Charge Chimeric Proteins Core Protein Corneal dystrophy Cystic Fibrosis DNA Data Development Disease Distal Dyes Engineering Face Figs - dietary Fluorescence Fluorescence Microscopy Gene Delivery Gene Expression Gene Proteins Gene Targeting Gene Transfer Genes Genetic Goals Heart Homing Hydrophobic Interactions Image Immune response Implant In Vitro Left Length Libraries Ligation Lipid Bilayers Lipids Liposomes Magnetism Malignant Neoplasms Mammalian Cell Measures Mesenchymal Stem Cells Microscopic Minor Modeling Myocardial Myocardial Ischemia N-terminal Nanotechnology Nature Non-Viral Vector Nutrient Organ Oxygen Peptides Phage Display Problem Solving Process Production Proteins Rattus Reporter Genes Side Site Specificity Staging Staining method Stains Structure Surface Technology Testing Tetanus Helper Peptide Therapeutic Therapeutic Agents Thick Tissues Toxic effect Transfection Tumor Tissue Ursidae Family VEGF165 VEGFA gene Vascular Endothelial Growth Factors Ventricular Viral Viral Genes Western Blotting abstracting angiogenesis base cancer therapy capillary cytotoxicity density design fd Phage gene therapy heart function hemodynamics immunogenicity improved in vivo interest magnetic field nanoparticle nanovector neoplastic cell neovascularization non-viral gene delivery non-viral gene therapy novel osteosarcoma particle retinal rods self assembly success targeted delivery therapeutic gene vector

项目摘要

Modified Project Summary/Abstract Section: Non-viral gene therapy is a promising approach to treating myocardial ischemia where the supply of oxygen and nutrients are blocked due to blockage in the blood vessels. Vascular Endothelial Growth Factor (VEGF) can trigger new blood vessel formation. Thus, one of the gene therapy strategies for treating myocardial ischemia is to graft mesenchymal stem cells (MSCs) with VEGF transfected in damaged heart tissue not only because the expressed VEGF can induce the formation of new blood vessels to supply the required oxygen and nutrients but also because MSCs can differentiate into heart muscle cells and revive the damaged tissue. Our long-term goal is to integrate biomolecular recognition and nanotechnology to build target-specific non-viral nano-vectors that can deliver VEGF gene to heart for treating myocardial ischemia. The objective of this application is to mimic the structure of phage to assemble target-specific peptides selected by phage display and a VEGF gene-tethered superparamagnetic nanoparticle into a phage-like nanoparticle for VEGF gene delivery. The overall hypotheses of this project are that phage display selected peptides that can target MSCs can be integrated into the VEGF gene-tethered superparamagnetic nanoparticles with cell-specific peptide motif protruding from the surface by a self-assembly process and the resultant multi-functional phage-like nanoparticle will have desired cell-specificity and improved efficiency of VEGF gene transfer into MSCs. Aim 1 is to select a peptide that can be specifically internalized into MSCs by using phage display technology. Aim 2 is to integrate cell-targeting peptides into VEGF gene-tethered superparamagnetic nanoparticles to build phage-like nanoparticles with cell-specific peptide motifs protruding from the surface through self-assembly. Aim 3 is to evaluate the stability, cytotoxicity, cell-specificity and transfection efficiency of the nanoparticles with and without an external magnetic field. Successful completion of this project will enable the development of a new gene therapy strategy for treating diseases that require VEGF expression to induce new blood vessel formation.

修改后的项目摘要/摘要部分：非病毒基因疗法是治疗心肌缺血的一种有前途的方法，心肌缺血是由于血管阻塞而导致氧气和营养物质的供应受阻。血管内皮生长因子（VEGF）可以触发新血管的形成。因此，治疗心肌缺血的基因治疗策略之一是将转染VEGF的间充质干细胞（MSC）移植到受损的心脏组织中，不仅因为表达的VEGF可以诱导新血管的形成以提供所需的氧气和营养，而且还因为间充质干细胞可以分化为心肌细胞并恢复受损组织。我们的长期目标是整合生物分子识别和纳米技术，构建靶向特异性非病毒纳米载体，将 VEGF 基因递送至心脏，治疗心肌缺血。该应用的目的是模拟噬菌体的结构，将噬菌体展示选择的靶标特异性肽和 VEGF 基因系留的超顺磁性纳米颗粒组装成噬菌体样纳米颗粒，用于 VEGF 基因递送。该项目的总体假设是，噬菌体展示选定的能够靶向 MSC 的肽可以通过自组装过程整合到 VEGF 基因拴系的超顺磁性纳米颗粒中，该纳米颗粒具有从表面突出的细胞特异性肽基序，并由此产生多功能噬菌体类纳米颗粒将具有所需的细胞特异性并提高 VEGF 基因转移至 MSC 的效率。目的1是利用噬菌体展示技术选择一种可以特异性内化到MSC中的肽。目标 2 是将细胞靶向肽整合到 VEGF 基因系留的超顺磁性纳米颗粒中，以通过自组装构建具有从表面突出的细胞特异性肽基序的噬菌体样纳米颗粒。目标 3 是评估纳米粒子在有或没有外部磁场的情况下的稳定性、细胞毒性、细胞特异性和转染效率。该项目的成功完成将有助于开发新的基因治疗策略，用于治疗需要 VEGF 表达诱导新血管形成的疾病。