Nanoparticle-based Artificial RNA Silencing Machine

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Non-Technical: The general goal of this project is to develop a new class of bioinspired nanomaterials (called Nanozymes or nanorobots). The PI has shown that this nanorobot technology complements the Nobel Prize-winning RNAi-based methods and has the potential to become a general experimental tool for fundamental biomedical research and an effective therapeutic tool for combating human diseases such as cancers and viral infections. However, the drawback in the current nanorobots due to the use of weakly bound wild-type RNase A has substantially slowed down their use in biomedical research and applications. To overcome this drawback, the PI plans to use bioengineered RNase A, which can be attached onto gold nanoparticles with strong multiple chemical bonds to construct a new generation of nanorobots. The research team will systemically maximize the target selectivity and enzymatic RNA cleavage activity of nanorobots through optimizing the sequence and structure of DNA oligonucleotides, the loading number of RNase A, and the size of gold nanoparticles over the next three years. These proposed research efforts are further integrated with educational efforts for training graduate and undergraduate students in multidisciplinary bio-nanotechnology research areas, which is important for future job creation and national economic growth. The educational efforts will also include educational outreach for high school students, with a focus on promoting their interests in science by improving their competitive ability in regional and international science and engineering fairs. In addition, the educational efforts are integrated with NSF-funded education programs (AGEP and REU) at the University of Florida. Technical: This project aims to develop a new class of bioinspired nanomaterials (called Nanozymes). Their preliminary results have shown that this nanozyme technology complements the RNAi (RNA interference)-based methods and can potentially become a general experimental tool for functional genomics and an effective therapeutic tool for combating human diseases such as cancer. However, these nanozymes were prepared using weakly bound wild-type RNase A, which have substantially slowed down the nanozyme's use in biomedical research and applications. To overcome this drawback, the PI plans to use recombinant RNase A, which will be attached onto gold nanoparticles with multiple gold-sulfur bonds, to construct a new generation of nanozymes. The research team will maximize the target selectivity and enzymatic RNA cleavage activity of nanozymes through systemically optimizing the sequence, structure and loading number of DNA oligonucleotides, the loading number of RNase A, and the size of gold nanoparticles over the next three years. These proposed research efforts will be further integrated with educational efforts. Graduate and undergraduate students will be trained in the proposed multidisciplinary research. Based on the proposed research, the PI plans to create a computer game (called NanoBot) as a tool to teach undergraduate and graduate students how to design effective nanozymes. In addition, the educational efforts include outreach to high school students and are also integrated with NSF-funded education programs (AGEP and REU) at the University of Florida.This project is co-funded by the Biomaterials Program in the Division of Materials Research and the Genetic Mechanisms Program in the Division of Molecular and Cellular Biosciences.