Showdown Between Two Groundbreaking Scientists Determines the Future of Genome Editing Technology

The United States Patent and Trademark Office (USPTO) currently has to resolve a billion dollar patent battle over a genome editing tool called CRISPR/Cas9. Jennifer Doudna of University of California, Berkley and Feng Zhang of the Broad Institute both claimed they made the major discoveries to the CRISPR system. With the potential to edit human genomes and cure genetic diseases at stake, the patent battle over CRISPR has become the center of attention for scientists worldwide.

CRISPR- or clustered regularly interspaced short palindromic repeats- is a genome editing technology that allows biologists and medical researchers to precisely edit parts of the genome along with a protein called Cas9, which acts as molecular scissors to cut DNA at specified locations [1]. Other genetic editing techniques such as transcription activator-like effector nuclease (TALEN) and zinc finger nuclease (ZNF) have been around since the early 2000s, but the simplicity and efficiency of CRISPR has led it to become the superior genome editing technology.

CRISPR’s genomic editing capability has a wide range of potential functions. One major application is genetically modifying foods and crops; CRISPR can be used to genetically modify the common white button mushroom to gain resistance to browning [2]. Additionally, CRISPR has the potential to cure genetic diseases and be used as a cancer treatment. While much research must be done before this is possible, many scientists think CRISPR can revolutionize therapeutics.

The CRISPR legal battle arose when the Broad Institute paid extra to expedite the patent process, giving them several patents that cover the use of CRISPR in eukaryotic organisms. This would allow them to use the technology in all multicellular organisms, ranging from mice to humans. Dr. Doudna and UC Berkeley filed an earlier patent application, but the Broad Institute argued that the application of CRISPR in eukaryotes was strictly speculation in Dr. Doudna’s work.

While the Broad Institute was the first to receive the patent, lawyers from UC Berkeley argued that Dr. Zhang and the Broad Institute overstated their discoveries in the patent application and never demonstrated or documented such genetic capabilities, specifically the use of tracrRNA- an RNA molecule that activates the DNA cutting segment of the CRISPR/Cas9 system. In addition, UC Berkeley lawyers pointed out that Dr. Zhang omitted several co-inventors from the patent application, which they argue was “deceitful intent”.

Both Dr. Doudna and Dr. Zhang were groundbreaking scientists even before the CRISPR discovery. Dr Doudna was awarded the prestigious Alan T. Waterman Award for her work in RNA crystallization and function while working at Yale University. Comparatively, Feng Zhang was featured in 35 Innovators Under 35 in 2013 for his work with optogenetics- a technique which uses light intensities to control light-sensitive cells- to cure psychiatric diseases in mouse models.

Despite their accolades, the influence of money cannot be overlooked, especially in a case this monumental. A 2015 report from the renowned global market research firm MarketsandMarkets projected the global genome editing market to be worth $3.5B by 2019 [3], a $2.7B increase from 2014. Additionally, the report stated, “By technology, the market is divided into CRISPR, TALEN, ZNF, antisense technology, and other technologies. Of these, CRISPR will account for the largest and the fastest-growing segment of the global genome editing market by 2019.”

Due to the financial potential, many scientists are investing in CRISPR-focused biotechnology companies. Dr. Doudna and Dr. Zhang, along with leading geneticist George Church, cofounded a biotechnology startup called Editas, which plans to use the CRISPR system to create personalized human therapeutics. The patent battle led to Dr. Doudna leaving this company and starting a rival biotech startup called Caribou Biosciences, Inc.

While the financial implications of the CRISPR breakthrough are immense, many people around the world are more concerned about the ethics behind the new technology. Since her CRISPR paper was published, Dr. Doudna has traveled all around the country discussing the issues of human modification with fellow scientists, congressmen and women, and even White House Officials. The major concerns are the implications of editing human eggs, sperm, and embryos.

 The Napa Bioethics Forum, a small consortium of scientists including Dr. Doudna, met in the spring of 2015 and have since urged researchers to avoid using CRISPR in human research until the precision and capabilities of the technology have been further explored [4].

Despite the recommendation by Dr. Doudna and the Napa Bioethics Forum, Chinese researchers led by Junjiu Huang, a genomic engineer at Sun Yat-sen University, have studied the use of CRISPR in nonviable embryos, or embryos that cannot result in live births. Only a fraction of the embryos maintained the genetic manipulation, while others showed incorrect cuts within the DNA[5]. These results point to the serious challenges with CRISPR and demonstrate that more research must be done before it is applied to human therapeutics.

The potential of CRISPR is promising, but no one knows how far the technology will progress. With the potential to make billions of dollars in human therapeutics on the line, the patent battle over CRISPR will only become more heated.

 

Bibliography:

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Begley, S. (2016). Clash of scientific titans: CRISPR hits the courts, with money and prestige at stake. STAT. https://www.statnews.com/2016/03/08/crispr-patent-fight/

Begley, S. (2016). In the CRISPR patent fight, the Broad Institute gains edge in early rulings. STAT. https://www.statnews.com/2016/03/18/crispr-patent-dispute/

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Gill C. (2016). Gene-edited mushroom created by Penn State researcher is changing GMO dialogue. Penn State News. http://news.psu.edu/story/405406/2016/04/19/research/gene-edited-mushroom-created-penn-state-researcher-changing-gmo

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Liang, P. et al. (2015). CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein & Cell 6. 363-372.

Marketsandmarkets.com (2015). Genome Editing / Genome Engineering Market by Application (Cell Line Engineering, Animal & Plant Genetic Engineering), Technology (CRISPR, Antisense, TALEN, Zinc Finger Nuclease) & End User (Biotechnology & Pharmaceutical, CRO) - Global Forecast to 2019.

Regalado, A. (2015). CRISPR Patent Fight Now A Winner-Take-All Match. MIT Technology Review. https://www.technologyreview.com/s/536736/crispr-patent-fight-now-a-winner-take-all-match/

Servick, K. (2016). Accusation of errors and deception fly in CRISPR patent fight. Science Community.

http://www.sciencemag.org/news/2016/03/accusations-errors-and-deception-fly-crispr-patent-fight

Yeadon, J., (2014). Pros and Cons of ZNFS,TALENS and CRISPR/CAS. The Jackson Laboratory Blog Post.  https://www.jax.org/news-and-insights/jax-blog/2014/march/pros-and-cons-of-znfs-talens-and-crispr-cas