I-Corps: Unlocking constraints on mammalian cell programming using synthetic DNA and evolutionary selection

The broader impact/commercial potential of this I-Corps project is the development of genetically engineered mammalian cell lines that enable cells to grow in the presence of environmental stressors such as the lack of specific nutrients or in the presence of toxic waste products. Such cells may lower the costs of mammalian cell-based manufacturing, which is used in the synthesis of products that are critical to modern medicine such as biologics and cellular therapies as well as in the manufacturing of products that may reduce the carbon footprint of global agriculture such as cultivated meat.

For example, cost parity of cultivated meat with conventional meat is not attainable with current technologies as over 95% of the cost of cultivated meat comes from the cost of adding recombinantly-produced growth factors to the culture medium to promote cell proliferation. Mammalian cells grown for cultured meat may be engineered to produce their own growth factors to reduce cost.

Genetically engineering resilience in mammalian cells has the potential to bring the cost of performing large-scale mammalian cell culture down to a fraction of present-day cost.

This I-Corps project is based on the development of a genetic engineering platform for mammalian cell programming. State-of-the-art technologies enable DNA writing into mammalian genomes at only the 10,000 base-pair scale. The proposed technology may allow genetic engineers to write >100,000 base-pairs into mammalian cells.

This ability may allow the encoding of more complex sets of instructions that can specify sophisticated cellular behaviors and overcome the existing size constraints on biological programming. In addition, the proposed technology may be used to solve the knowledge constraint, i.e., selecting from an almost infinite number of equally (un)likely potential solutions to engineer a particular behavior.

The platform is designed to rapidly prototype and test thousands of solutions in parallel. This work is based on technical results demonstrating the ability to enable mammalian cells to grow in the absence of valine, a canonically essential amino acid.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.