Gene delivery vectors inspired from the structure and assembly process of target-recognizing phage

受目标识别噬菌体结构和组装过程启发的基因传递载体

• 批准号: 0854465
• 负责人: Chuanbin Mao
• 金额: $ 30万
• 依托单位: University of Oklahoma Norman Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0854465&HistoricalAwards=false
• 关键词: Gene; delivery; vectors; inspired; structure

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)0854465MaoGene therapy relies on the development of vectors that can carry therapeutic genes to target cells. Non-viral vectors can avoid the safety issue inherent to the viruses, but lack the capability of recognizing target cells and have low efficiency of transferring gene into the target cells. This project will mimic the cell-recognition capability of a nanoparticle-like virus called phage, which can specifically infect bacteria and is non-toxic to human beings, to develop a novel nanoparticle that can serve as a non-viral gene delivery vector. Mesenchymal stem cells are used as a model cell type to test the capability of the gene delivery into the target cells by the non-viral vector. This project will integrate cell-targeting peptides and DNA-tethered inorganic nanoparticles to form a composite nanoparticle with the cell-targeting peptides presented on the nanoparticle surface by using a chemical process that mimics the assembly process of the nanoparticle-like virus. Then the capability of gene transfer by the resultant nanoparticles is evaluated by using a fluorescent reporter gene for optically detecting gene expression. This transformative project will develop peptide-modified inorganic nanoparticles that can deliver therapeutic gene to mammalian cells. The technique developed in this project can be extended to form nanoparticles that can deliver other cargos to mammalian cells. The novel nanoparticles represent virus-mimicking non-viral vectors and can find potential applications in treating diseases by gene therapy.This project will have broader impacts on bioengineering, materials science, chemistry, biology, and nanomedicine. It will generate a new biomimetic strategy for developing target-specific nanoparticles that can deliver genes and drugs to target sites for disease diagnosis and treatment. It will provide insights into the biology of virus assembly processes. The PI will integrate this project into the development of a new bionanotechnology class and train graduate students to have multidisciplinary skills. He will attract undergraduate students, community college and high school students to participate in this project. He will also recruit Native American students to work on this project and disseminate bionanotechnology knowledge to minority students and the general public by collaborating with local educators and state government agencies.

该奖项是根据2009年美国复苏和再投资法案（公法111-5）0854465 Mao资助的。非病毒载体可以避免病毒固有的安全性问题，但缺乏识别靶细胞的能力，并且将基因转移到靶细胞中的效率低。该项目将模拟一种称为噬菌体的纳米颗粒状病毒的细胞识别能力，这种病毒可以特异性感染细菌，对人类无毒，以开发一种新型纳米颗粒，可以作为非病毒基因传递载体。间充质干细胞用作模型细胞类型以测试通过非病毒载体将基因递送到靶细胞中的能力。该项目将整合细胞靶向肽和DNA系留的无机纳米颗粒，通过使用模拟纳米颗粒样病毒组装过程的化学过程，形成具有呈现在纳米颗粒表面的细胞靶向肽的复合纳米颗粒。然后，通过使用用于光学检测基因表达的荧光报告基因来评价所得纳米颗粒的基因转移能力。这个变革性的项目将开发肽修饰的无机纳米颗粒，可以将治疗基因传递到哺乳动物细胞。该项目开发的技术可以扩展到形成纳米颗粒，可以将其他货物运送到哺乳动物细胞。这种新型的纳米粒子代表了病毒模拟的非病毒载体，在基因治疗疾病方面具有潜在的应用前景，将对生物工程、材料科学、化学、生物学和纳米医学产生广泛的影响。它将产生一种新的仿生策略，用于开发靶向特异性纳米颗粒，可以将基因和药物输送到疾病诊断和治疗的靶点。它将提供深入了解病毒组装过程的生物学。PI将把这个项目整合到一个新的生物纳米技术课程的开发中，并培养研究生具备多学科技能。他将吸引本科生、社区学院和高中生参与这个项目。他还将招募美国原住民学生参与该项目，并通过与当地教育工作者和州政府机构合作，向少数民族学生和公众传播生物纳米技术知识。