Bone-seeking and cell-targeting non-viral vectors for BMP-2 gene delivery

用于 BMP-2 基因传递的骨寻找和细胞靶向非病毒载体

基本信息

批准号：
7576668
负责人：
Chuanbin Mao
金额：
$ 7.5万
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：
2009-07-17 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7576668
关键词：
Adenoviruses Adopted Affinity Automobile Driving BMP2 gene Bacteriophages Binding Biological Biomimetics Bone Diseases Bone Morphogenetic Protein Gene Bone Morphogenetic Proteins Bone Regeneration Bone Tissue Brain Breast C-terminal Capsid Proteins Cell membrane Cells Charge Complementary DNA Core Protein DNA Data Dependovirus Disease Distal Durapatite Encapsulated Ensure Evaluation Exhibits Figs - dietary Fluorescence Fluorescence Microscopy Fracture Gene Delivery Gene Proteins Gene Transduction Agent Genes Genetic Goals Harvest Heart Hydrophobic Interactions Immune response Implant In Vitro Injury Length Libraries Lipid Bilayers Lipids Liposomes Mammalian Cell Mesenchymal Stem Cells Minerals Minor Musculoskeletal N-terminal Nanotechnology Natural regeneration Non-Viral Vector Organ Osteogenesis Imperfecta Patients Peptides Phage Display Phase Plasmids Proteins Random Peptide Libraries Rest Retroviridae Side Site Specificity Staging Staining method Stains Structure Surface Technology Testing Tetanus Helper Peptide Therapeutic Tissues Toxic effect Transfection Tumor Tissue Viral Viral Genes Viral Vector Virus base bone bone cell bone morphogenetic protein 2 design fd Phage gene therapy in vivo interest intravenous injection liposome vector nanoparticle non-viral gene delivery novel particle repaired retinal rods self assembly success vector

项目摘要

DESCRIPTION (provided by applicant): Gene therapy has emerged as a promising strategy for bone repair and regeneration. The key to its success is to deliver the genes of interest to the target bone fracture site that can be expressed at suitable levels. Both ex vivo and in vivo gene therapy strategies have been proposed. In the ex vivo strategy, target cells such as mesenchymal stem cells (MSCs) are harvested from the patient, genes of interest such as bone morphogenetic protein (BMP) gene carried by a vector are delivered to the target cells under in vitro conditions, and then the target cells are implanted into the site of injury. In the in vivo strategy, genes of interest carried by a vector are delivered to the target site by intravenous injection or directly implanted to the site of injury. Thus an ideal gene delivery vector should be bone-seeking and cell-targeting. Our long-term goal is to integrate the naturally evolved biological recognition and nanotechnology to build target-specific non-viral gene vectors for bone regeneration by gene therapy. The objective of this particular application is to form and evaluate bone-seeking and cell-targeting non-viral vectors for virus-like site-specific delivery of BMP-2 gene. The overall hypothesis of this project is that bone-seeking and cell-targeting peptides identified by a virus-based selection technology can biomimetically self-assemble with the BMP-2 gene-bearing nanoparticles to form bone-seeking and cell-targeting virus-like non-viral vectors for site-specific BMP-2 gene delivery. The following specific aims are designed to test our central hypotheses: (1) Selection of bone-seeking and cell-targeting peptides from a virus-based random peptide library; (2) Biomimetic assembly of BMP-2-gene-bearing nanoparticles and the bone-seeking and cell-targeting peptides to form bone-seeking and cell-targeting non-viral vectors; and (3) Evaluation of in vitro BMP-2 gene delivery by the bone-seeking and cell-targeting non-viral vectors. Successful completion of this project will discover a bone-seeking and cell-targeting peptide and produce a novel non-viral gene delivery vector that exhibits high transfection efficiency and bone cell/tissue-specificity. Such vectors can be used for the repair and regeneration of musculoskeletal tissues and treatment of genetic based bone diseases such as osteogenesis imperfecta by gene therapy.

描述（由申请人提供）：基因疗法已成为骨修复和再生的有前途的策略。成功的关键是将感兴趣的基因传递给可以在合适水平表达的目标骨断裂部位。已经提出了离体和体内基因治疗策略。在离体策略中，从患者那里收集了诸如间充质干细胞（MSC）的靶细胞，感兴趣的基因，例如由载体携带的骨形态发生蛋白（BMP）基因在体外条件下输送到靶细胞，然后将靶细胞植入受伤部位。在体内策略中，载体携带的感兴趣的基因通过静脉注射或直接植入受伤部位。因此，理想的基因递送载体应该是寻求骨和细胞靶向的。我们的长期目标是将自然发展的生物学识别和纳米技术整合起来，以通过基因治疗来建立靶标特异性的非病毒基因量来进行骨骼再生。该特定应用的目的是形成和评估用于病毒样的BMP-2基因递送的病毒样品特异性递送的寻求骨和细胞靶向的非病毒载体。该项目的总体假设是，通过基于病毒的选择技术鉴定出的寻求骨和细胞靶向肽可以与BMP-2基因含有基因的纳米颗粒在生物相视频上进行自我组装，以形成骨寻求骨和细胞靶向病毒式的非病毒式非病毒式载体，以实现特定于特异性的BMP-2基因递送。以下特定目的旨在测试我们的中心假设：（1）从基于病毒的随机肽库中选择寻求骨和细胞靶向肽；（2）BMP-2基因纳米颗粒以及寻求骨和细胞靶向肽的仿生组装，形成寻求骨和细胞靶向的非病毒载体；（3）评估通过寻求骨和细胞靶向非病毒载体的体外BMP-2基因递送的评估。该项目的成功完成将发现寻求骨和细胞靶向肽，并产生一种新型的非病毒基因递送载体，该媒介表现出高转染效率和骨细胞/组织特异性。这种载体可用于修复和再生肌肉骨骼组织和通过基因治疗等遗传性骨疾病（例如骨生成不完美）的治疗。