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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)：基因治疗已经成为一种很有前途的骨修复和再生策略。其成功的关键是将感兴趣的基因输送到目标骨折部位，并在合适的水平上表达。已经提出了体外和体内的基因治疗策略。在体外策略中，从患者体内获取间充质干细胞(MSCs)等靶细胞，在体外条件下将载体携带的骨形态发生蛋白(BMP)基因等感兴趣的基因输送到靶细胞，然后将靶细胞植入损伤部位。在体内策略中，载体携带的感兴趣基因通过静脉注射传递到目标位置或直接植入损伤位置。因此，理想的基因递送载体应该是寻骨和细胞靶向。我们的长期目标是整合自然进化的生物识别和纳米技术，构建靶向特异性的非病毒基因载体，用于基因治疗的骨再生。这一特殊应用的目的是形成和评价骨搜索和细胞靶向的非病毒载体，用于病毒样部位特异性递送BMP-2基因。该项目的总体假设是，通过基于病毒的选择技术识别的骨搜索和细胞靶向多肽可以仿生地与BMP-2基因纳米颗粒自组装，形成骨搜索和细胞靶向病毒样非病毒载体，用于位点特异性BMP-2基因的传递。为了验证我们的中心假设，我们设计了以下特定目标：(1)从基于病毒的随机肽库中选择骨搜索和细胞靶向多肽；(2)BMP-2基因纳米颗粒与骨搜索和细胞靶向多肽的仿生组装，以形成骨搜索和细胞靶向非病毒载体；以及(3)骨搜索和细胞靶向非病毒载体体外输送BMP-2基因的评价。该项目的成功完成将发现一种寻骨和细胞靶向的多肽，并产生一种新型的非病毒基因传递载体，具有高的转染率和骨细胞/组织特异性。这些载体可用于肌肉骨骼组织的修复和再生，以及通过基因治疗治疗成骨不全等遗传性骨疾病。