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

该奖项是根据2009年美国复苏和再投资法案（公法111-5）0854465MaoGene治疗依赖于能够携带治疗基因到靶细胞的载体的发展。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，将基因转移到靶细胞的效率较低。这个项目将模仿一种叫做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地感染细菌，对人类无毒，从而开发出一种可以作为非病毒基因传递载体的新型纳米颗粒。间充质干细胞被用作模型细胞类型来测试基因通过非病毒载体传递到靶细胞的能力。该项目将整合细胞靶向肽和dna系缚的无机纳米颗粒，通过模拟纳米颗粒样病毒的组装过程的化学过程，将细胞靶向肽呈现在纳米颗粒表面，形成复合纳米颗粒。然后利用荧光报告基因光学检测基因表达来评价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。在这个项目中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中。这种新型纳米颗粒代表了模拟病毒的非病毒载体，可以在基因治疗疾病方面找到潜在的应用。该项目将对生物工程、材料科学、化学、生物学和纳米医学产生更广泛的影响。它将产生一种新的仿生策略，用于开发靶向纳米颗粒，这种纳米颗粒可以将基因和药物运送到疾病诊断和治疗的靶点。它将为病毒组装过程的生物学提供见解。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，并培养研究生具有多学科技能。他将吸引本科生、社区学院和高中生参与这个项目。他还将招募美国土著学生参与这个项目，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。

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.