Proteins are becoming increasingly important drugs to treat and prevent diseases. In fact, among the current top ten best selling drugs in the world, eight of them are protein-based. At present, almost all proteins are manufactured by living organisms. Unfortunately, using living organisms to produce proteins has various limitations and problems including low production rate and high set-up cost. Most severely, living organisms need to be sufficiently fed and well taken care of, which has not been easy on an industrial scale. In this project, the researchers led by Prof. Dan Luo at Cornell University will develop a first-ever, nanotechnology-enabled protein manufacturing process without using live cells. The researchers will use nanoclay crystals along with DNA as starting materials; nanoclay is an inexpensive material that can be easily scaled up, and DNA provides the blueprint for the desired proteins. Together, nanoclay and DNA will be processed into billions of teeny tiny donuts such that proteins can be manufactured through these donuts efficiently and continuously, all without living organisms and on a large scale. If successful, this research will become an entirely new platform where proteins, including those that cannot be produced by living organisms, can be manufactured relatively inexpensively on a large scale.
The goal of this research project is to address major issues for cell-free protein manufacturing, which is recognized as a critical manufacturing challenge. The investigators have established exciting results in: 1) DNA hydrogels to produce proteins without live cell with 20X enhanced throughput rates; 2) use of nanoclay crystals to protect DNA and enhance protein productions; 3) NanoClay-DNA (NanoCD) microdonuts to form a manufacturing platform. The investigators covers DNA bionanotechnology, electro hydrodynamic processing and large-scale system design, fluidic dynamics and interface stability, and protein engineering. The industrial partners, TeraPore Technologies and DuPont, cover issues for protein purification and outreach and future commercialization. The proposed research, if successful, will become a platform technology that enables NanoCD-based, continuous, scalable and cell-free manufacturing of most proteins. The project will also be a demonstration of integrating hierarchical materials in a scaled-up manufacturing process: from molecular-scale DNA to nano-scale clay to micro-scale electrosprayed micro-donut gel particles and to macro-scale continuous bioreactors.
This research will have significant societal impact and benefits. First, it translates both nanomaterials (nano-clay) and nanobiotechnology (DNA nanotech) into a large-scale manufacturing platform that may replace the often slow, costly, and labor-intensive conventional cell-based protein productions. In addition, these systems will pave the way for manufacturing many more different or difficult-to-express proteins that will be urgently needed. The successful completion of this research project will have become a powerful, economic and universal technology that will be adopted by both academics and pharmaceutical/biotechnology industries. This research will also impact education with a carefully-designed, feasible, and integrated three-pronged plan: (1) Outreach to high school students; (2) Expand undergraduate and graduate students' experience and horizons including international research experience and industrial experience; and (3) Increase the recruitment of under-represented minority and female engineering students.
