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

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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.