Pilot Project for Ultra-Safe Cell Lines Launched in 2018 GP-write

The Center for Excellence in Engineering Biology and the leadership of Genome Project-write (GP-write) announced a grand-scale community-wide project, to develop “ultra-safe cells”, at the GP-write 2018 annual meeting in Boston, Massachusetts, on 1 May.

By Joanne Shih

In the project, an ultra-safe cell line is characterized with the ability of resisting natural viruses and potentially radiation, freezing, aging and cancer, and aim to design the cell line to be applied to many biomedical applications, from production of biologics, to modelling cell and tissue behaviours, to therapeutic applications.

The project was originally designed to synthesize an entire human genome. However, with a lack of financial support and gaps between theory and currently viable technique, scientists took a smaller gait to aim at a more technically achievable near-term goal. Instead of synthesizing the entire 3 billion DNA base pairs of human genome, the project will now focus on recoding the genome to produce virus-proof cell line.

“Ultra-safe cells could have a major impact on human health,” said, Dr. George Church, professor at Harvard Medical School and one of four members of the GP-write Leadership Group. Mentioning the potential hazard of viral contamination in pharmaceutical manufacture, Church pointed the economic value of this promising tool, “Ultra-safe cells could make pharmaceuticals safer, cheaper and more reliable.”

Another leading member of GP-write, Dr. Jef Boeke, Director of the Institute for Systems Genetics at New York University Langone Health, said, “The ultra-safe cell lines, made using technologies broadly applicable to plant, microbial and mammalian species, are aimed at complete resistance to all viruses and prions, and partial resistance to senescence and cancer, plus biocontainment.”

Detailed properties of the cell line are outlined in the project proposal including virus resistant, cancer resistant, and immuno-negative which theoretically mean the cell line can resist viruses via sense codon/tRNA recoding, will have P53 and other tumor suppressors re-engineered to minimize chance of deleterious mutations, and will be engineered to minimize immune rejection.

Creating cell lines with specific properties relies on the technique of DNA recoding. Even with the previous research in recoding bacterial genome, the current process of synthesizing artificial genome is very slow. In order to achieve the goal of developing an ultra-safe cell line in the near future, the Wyss Institute and biopharmaceutical company Cellectis announced a collaboration at the GP-write Scientific Working Meeting. Cellectis will give the Church lab access to Cellectis proprietary TALEN gene editing technology that has the capacity of modifying DNA code with high specificity and across an entire genome. The GP-write organizers hope to complete their work within 10 years.

Reference

1. Nature 557, 16-17 (2018) doi: 10.1038/d41586-018-05043-x
2. Boeke, J. D. et al. Science 353, 126–127 (2016).
3. Marc J. L. et al. Science 342, 357-360 (2013).
4. http://engineeringbiologycenter.org
5. http://www.engineeringbiologycenter.org/press/may2018.pdf

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