Genome editing has been an extremely interesting field the last 10 years, primarily because recently, the first genome editing tools for human cells became available to the world via Sangamo Biosciences and Sigma-Aldrich (2008). CRISPR has rapidly accelerated the R&D trajectory begun by ZFNs by making synthesis of targeted nucleases extremely fast and simple. Challenges still exist in genome editing methods which use human cells in laboratory culture; human cell types are extremely diverse in their behavior and do not always like intrusions by ZFN or CRISPR molecules. Addressing these varied human cellular personalities is now a major challenge before many scientists and medical researchers.
As nature itself has shown us via evolution and natural selection, there are virtually endless possibilities for genome editing in the living world. It is exciting to see creative and logical genetic concepts, which were once only a dream, become a reality in the form of new healthcare options like cancer immunotherapy, which uses genome edited T cells to attack specific cancers. I see our contribution as enabling genome editing in cellular systems where there is a great societal benefit. We made a huge step for human cellular engineering with commercialization of ZFNs in 2008, and we hope to continue this work with new technologies such as CRISPR; and who knows what is next? We are excited every day to find out.
How living organisms manage their genomes to defend themselves and thrive never stops to amaze me. There are single cell organisms, such as the ciliate Oxytricha, which unscrambles its single large genome into 16,000 tiny nanogenomes during its cell cycle. Why and how does that happen? Fundamental academic research into molecular biology (DNA, proteins, small biochemicals, etc.) has uncovered the function of group II introns (Targetrons), zinc fingers (ZF), transcription activator-like effectors (TALs), and CRISPR systems. The genome editing field would not exist without the discovery and characterization of these DNA-associated molecular machines. Today, modification of these systems is a highly active R&D field driving new innovations in cancer immunotherapy, agriculture, and the basic biological sciences.
I chose to work for our company because at their highest corporate executive levels, they are strongly vocal in their support of science, curiosity, and innovation. That executive-level verbal affirmation is inspiring to Merck KGaA, Darmstadt, Germany's scientists, especially since it is also followed by action via the endless opportunities our company makes for collaboration (both within and outside the company) and education outreach so that we can pass along our enthusiasm to young aspiring scientists. While it is clear we need to be financially profitable as a corporation, day-to-day at our company that financial goal is deeply intertwined with a true interest in science.
How living organisms manage their genomes to defend themselves and thrive never stops to amaze me.
Joined Merck KGaA, Darmstadt, Germany: 2015
Key research fields and topics:
- Genome Editing
- Zinc Finger Nucleases (ZFNs)
- Directed molecular evolution.
Prizes and awards:
- The Promise Award, Merck KGaA, Darmstadt, Germany, 2017, Foundational CRISPR Integration Patents.
- The Promise Award, Merck KGaA, Darmstadt, Germany, 2016, CRISPR and Genome Editing Technology.
- The Promise Award, Merck KGaA, Darmstadt, Germany, 2015, CRISPR and Genome Editing Technology.
- President’s Innovation Award, Sigma-Aldrich, May 2015, CRISPR and Genome Editing Technology.Featured in Nature Methods “Author File”, September 2011. Overview of ZFN and ssDNA oligo publication in the same issue.
CV & Scientific activities
- Chen F, Ding X, Feng Y, Seebeck T, Jiang Y, Davis GD. Targeted activation ofdiverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting. Nat Commun. 2017 Apr 7;8:14958.
- Metzakopian E, Strong A, Iyer V, Hodgkins A, Tzelepis K, Antunes L, Friedrich MJ, Kang Q, Davidson T, Lamberth J, Hoffmann C, Davis GD, Vassiliou GS, SkarnesWC, Bradley A. Enhancing the genome editing toolbox: genome wide CRISPR arrayedlibraries. Sci Rep. 2017 May 22;7(1):2244.
- Chen F, Pruett-Miller SM, Davis GD. Gene editing using ssODNs with engineered endonucleases. Methods Mol Biol. 2015;1239:251-65.
- Duda et al. "High-efficiency genome editing via 2A-coupled co-expression of fluorescent proteins and zinc finger nucleases or CRISPR/Cas9 nickase pairs." Nucleic Acids Research 42.10. 2014. e84-e84.
- Chen, F., Pruett-Miller, S.M., Huang, Y., Gjoka, M., Duda, K., Taunton, J., Collingwood, T.N., Frodin, M., & G.D. Davis. 2011. High frequency genome editing using ssDNA oligonucleotides with zinc finger nucleases. Nature Methods. 8(9):753.
- DeKelver et al. 2010. Functional genomics, proteomics, and regulatory DNA analysis in isogenic settings using zinc finger nuclease-driven transgenesis into a safe harbor locus in the human genome. Genome Res. 8:1133-42.
- Geurts et al. 2009. Knockout rats via embryo microinjection of zinc-finger nucleases. Science. 325(5939):433.
- Davis, G.D. and K.J. Kayser. Chromosomal Mutagenesis. Methods Mol Biol (435). 2008. Coordinated author participation and edited 16 Chapters on targeted genome editing applications.
- Rodriguez, S.A., Yu, J.J., Davis, G., Arulanandam, B.P., Klose, K.E. Targeted inactivation of Francisella tularensis genes by group II introns. 2008. Appl Environ Microbiol. 74(9):2619-26.
- Cui, X., Davis, G. Mobile group II intron targeting: applications in prokaryotes and perspectives in eukaryotes. 2007. Front Biosci. 2007. 12:4972-85. Review.
- Davis, G.D. and R.G. Harrison. 2003. Discovery of New Fusion Protein Systems Designed to Enhance Solubility in Escherichia coli. Methods in Molecular Biology. 205:141-54.
- Davis, G.D., Novy, R.E., Drott, D.W. and R.G. Harrison. 2002. The use of NusA fusion proteins to improve recombinant protein solubility in conventional and high-throughput applications. Gene Cloning & Expression Technologies, M.P. Weiner and Q. Lu(Eds.), Eaton Publishing, Westborough, Massachusetts (Book Chapter).
- Davis, G.D., Elisee, C., Newham, D. and R.G. Harrison. 1999. New Fusion Protein Systems Designed to Increase Soluble Cytoplasmic Expression of Heterologous Proteins in Escherichia coli. Biotechnology and Bioengineering. 65(4):382-8.
- Davis, G.D. and R.G. Harrison. 1998. Rapid Screening of Fusion Protein Recombinants by Measuring Effects of Protein Overexpression on Cell Growth. Biotechniques. 24(3):360-2.
- Haught, C., Davis, G.D., Subramanian, R., Jackson, K.W. and R.G. Harrison. 1998. Recombinant Production and Purification of a Novel Antisense Antimicrobial Peptide in Escherichia coli. Biotechnology and Bioengineering. 57(1): 55-61.
Several pending patent applications related to genome editing and detection with ZFNs, CRISPR, donor molecules, and related genome editing processes.
- European Patent 3138910, CRISPR-based Genome Modification and Regulation. Sept 20, 2017. As of March 2018, similar allowances in Australia, Canada, Singapore, Israel, and South Korea.
- U.S. Patent 7,919,322. Spears, M., Davis, G.D., and K. Kayser. 2011. Targeted deletions using retroelement-mediated placement of recombination sites. Assigned to Sigma-Aldrich.
- U.S. Patent 7,399,620. Spears, M., Davis, G.D., and H. George. 2008. Polypeptides and bacterial strains for increased protein production. Assigned to Sigma-Aldrich.
- U.S. Patent 6,383,755. Davis, G.D. and H. Wurst. 2002. Methods and Kits for Determining the Fidelity of Polymerase Chain Reaction Conditions. Assigned to Clontech Laboratories.
- U.S. Patent 5,989,868. Harrison, R.G. and G.D. Davis. 1999. Fusion Protein Systems Designed to Increase Soluble Cytoplasmic Expression of Heterologous Proteins in Escherichia coli. Assigned to the University of Oklahoma. Licensed to Novagen Inc. in 1999, followed by product release.
- Wind River Conference on Prokaryotic Biology, June 7-10, 2006, Talk titled “Chromosomal engineering using targeted group II introns (Targetron)”.
- Boston Bacterial Meeting, June 21-22, 2007, Talk title “Enabling Microbial Functional Genomics using Targeted Group II Introns”.
- 14th Annual International Meeting on Microbial Genomics Lake Arrowhead, Sept 24-28, 2006. Talk title “Use of Group II Introns for Large Scale Engineering of Chromosomes”.
- Gordon Conference on Signal Transduction within the Nucleus. Feb 27-Mar 4, 2011. Talk title “Modulation of endogenous kinase activity in human cells via codon editing with zinc finger nucleases”.
- Conference on Genome Engineering, June 20-22, 2011, Singapore. Talk title "Targeted Genome Editing Using ssDNA Oligos and Zinc Finger Nucleases".
- FASEB, Genome Engineering - Research & Applications, Lucca, Italy, Sept. 2-7, 2012. Talk title “Targeted genome editing using ZFNs with ssDNA oligos and alternative donor formats”.
- Keystone: Precision Genome Engineering and Synthetic Biology, Breckenridge, CO, March 17-22, 2013. Chaired session on Designer Engineering of Genomes. Oral presentation entitled "Enrichment of genome edited cell populations by transient co-expression of fluorescent proteins and ZFNs".
- Plant Targeted Genetic Modification Oversight (TagMo). June 7, 2013. University of Minnesota. Organized by Dan Voytas and Jennifer Kuzma.
- Genome Engineering and Synthetic Biology, VIB, Ghent, Belgium, Sept. 16-17, 2013. Talk entitled "Genome Editing in Bacterial and Mammalian Cells using Group II Introns, CompoZr ZFNs, and CRISPR-Cas Systems".
- FASEB, Genome Engineering - Research & Applications. Summer 2014. Session chair and speaker.
- Society for Laboratory Automation and Screening, Cellular Technologies, Genome Editing, Session Chair and speaker, Feb 2017.