Organizing genome engineering for the gigabase scale
Bryan A. Bartley, Jacob Beal, Jonathan R. Karr, Elizabeth A. Strychalski
Engineering an organism's entire genome enables large-scale changes in organization, function, and environmental interactions, with significant implications for industrial, medical, and environmental ap- plications broadly. Improvements to DNA synthesis and organism engineering have already enabled re- engineering of simple organisms with megabase genomes, such as Escherichia coli and Saccharomyces cerevisiae. Recently, researchers affiliated with the Genome Project- write consortium have proposed a variety of projects aiming to develop human cell lines with engineered genomes. However, substan- tial remaining challenges must be overcome to realize engineering of complex organisms with gigabase genomes. Toward this end, we examined the emerging workflow for genome engineering to identify potential scaling bottlenecks to gigabase engineering, propose potential solutions, and highlight gaps that require further research. Beyond the well-known challenges of manipulating DNA at the gigabase scale, we find that prohibitive challenges remain for coordinating the flow of models, designs, constructs, and measurements across the large teams and technological systems that will likely be required for genome engineering. While we find clear existing paths for developing technologies for representing and exchang- ing information at the gigabase genomic scale, we also find major open questions around quality control and experimental data curation, a need for more fundamental research to integrate modeling and design, and a need for new legal and contractual infrastructure to enable multi-institution collaboration.
, Beal, J.
, Karr, J.
and Strychalski, E.
Organizing genome engineering for the gigabase scale, Nature Communications, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=928506
(Accessed September 23, 2021)