Pre-existing technological core and roots for the CRISPR breakthrough.

This paper applies objective methods to explore the technological origins of the widely acclaimed CRISPR breakthrough in the technological domain of genome engineering. Previously developed patent search techniques are first used to recover a set of patents that well-represent the genome editing domain before CRISPR. Main paths are then determined from the citation network associated with this patent set allowing identification of the three major knowledge trajectories. The most significant of these trajectories for CRISPR involves the core of genome editing with less significant trajectories involving cloning and endonuclease specific developments. The major patents on the core trajectory are consistent with qualitative expert knowledge of the topical area. A second set of patents that we call the CRISPR roots are obtained by finding the patents directly cited by the recent CRISPR patents along with patents cited by that set of patents. We find that the CRISPR roots contain 8 key patents from the genome engineering main path associated with restriction endonucleases and the expected strong connection of CRISPR to prior genome editing technology such as Zn finger nucleases. Nonetheless, analysis of the full CRISPR roots shows that a very wide array of technological knowledge beyond genome engineering has contributed to achieving the CRISPR breakthrough. Such breadth in origins is not surprising since "spillover" is generally perceived as important and previous qualitative studies of CRISPR have shown not only technological breadth in origins but scientific breadth as well. In addition, we find that the estimated rate of functional performance improvement of the CRISPR roots set is about 9% per year compared to the genome engineering set (~4% per year). These estimates indicate below average rates of improvement and may indicate that CRISPR (and perhaps yet undiscovered) genome engineering developments could evolve in effectiveness over an upcoming long rather than short time period.