Turning a Natural Phenomenon into a Gene Editing Powerhouse: CRISPR Pioneer, Doudna, at Stanford’s Johnson Symposium

The CRISPR cake

Last week, I celebrated my eighteenth birthday. My dorm threw me in the shower, per Stanford tradition, and baked me a cake. The cake was made of Rice Krispies Treats – a direct pun on one of my greatest interests in science: CRISPR. My fascination with CRISPR started when I was a freshman in high school, and continued in the form of a four-year research project that studied the use of CRISPR to preferentially target cancerous cells. I had used CRISPR So, when I found out that Jennifer Doudna, a leading figure in the so-called “CRISPR Revolution,”[1] was presenting at Stanford’s William S. Johnson Symposium, I immediately jumped on the opportunity to attend.

JiwooFig1

Figure 1: A “CRISPR” birthday cake, courtesy of my dorm, West Lagunita, and its “birthday fairy”, Sophia Colello

From humble origins to gene editing breakthrough

crispr

Figure 2: Artistic representation of CRISPR as a pair of molecular scissors cutting DNA “Molecular Scissors Animation” is courtesy of Jiwoo Lee

CRISPR is a biotechnology tool that can modify DNA, or the sequences of molecules that make up the essential genetic information of all living things. The complete set of DNA in an organism makes up what we call the genome, and within that genome resides the genes that define the characteristics of all living organisms. Currently, scientists are using CRISPR to engineer the genomes of cells, plants, and even animals. The gene editing form of this novel technology has two main components: scissors and a GPS system. The “scissors” are actually an enzyme – or a molecular catalyst – that can cut DNA in a precise, rapid manner. The biological “GPS” is a molecule of RNA that guides the enzyme to a specific location on the DNA strand of interest. Think of RNA as the messenger for the flow of genetic information: it is the “middle man” that transfers the information encoded by DNA to the actual “building blocks” of a cell – proteins. This process from DNA to RNA to protein is called the central dogma, and is what governs the genetic basis of all living organisms.

RNA is the complement to DNA, meaning that its sequence can match up with the DNA in a process called base pairing. After attaching to the CRISPR enzyme, the RNA can pair up with a specific segment of DNA, and thus leading the editing system to the gene of interest. The enzyme carries out a precise cleavage of the DNA strands. The natural repair mechanisms of the cell can then be leveraged to insert, delete, or otherwise modify genetic information. The concept of CRISPR and its gene editing capabilities seem straight out of a science fiction novel – surely not something that could have arisen from nature. I was excited to learn how this nearly inconceivable tool came to be.

The woman behind the revolution

As I filed into the auditorium of the Sapp Center, questions buzzed around my head. Who was the genius behind the discovery of CRISPR? What did it take to discover arguably one of the greatest biological technologies of all time?

 

 

JiwooFig3

Figure 3: Dr. Jennifer Doudna started with a degree in biochemistry and an avid fascination with RNA. It was this fascination that lead her to becoming one of the most prominent CRISPR researchers today. Jennifer Doudna” by Jussi Puikkonen/KNAW is licensed by CC BY 2.0

As Jennifer Doudna took the microphone, I could hear the anticipation of the audience, eager to learn about the woman behind the magic. Today, CRISPR is, as Doudna says, a “household word”. However, it has not always been that way. Doudna’s journey started off as an undergraduate student with an avid interest in biochemistry. Rather than study the starting material, DNA, or the end product, protein, Doudna chose to study “the boring part in the middle”: RNA. While she was studying the chemical properties of RNA, she was also working on a curiosity-driven side project that stemmed from a novel idea that the bacterial adaptive immune system could be leveraged for advancements in biotechnology.Leveraging natural phenomenon

When you get sick, it is most likely that a foreign invader, usually a virus, has attacked your body. After fighting back and killing the virus, your body’s immune system can actually remember the invader so that it is better prepared for a future attack. Similarly, bacteria can also be invaded by viruses. Though it is thought to be a biologically unadvanced organism, bacteria have also developed ways to fight against foreign invaders.

When bacteria are invaded by viruses, they steal pieces of DNA from the virus and store it as short, palindromic sequences in their own bacterial genome. That way, when bacteria are attacked by the same viruses in the future, they have the prior knowledge required to quickly employ biological molecules, like enzymes, to kill those particular viruses. It was this deceptively simple natural phenomenon that soon became the center of a massive biotechnology revolution.

The future of CRISPR

Funny enough, Jennifer Doudna recalled wondering whether her work would ever have an impact. She even took a leave from academia to work in industry, but was not gone long before realizing she was “built to be in an academic environment.” At the Johnson Symposium, Doudna described the moment when she and her lab members drew out the concept of CRISPR on a white board and it dawned on them: “This could be a very powerful technology.”

Their dreams for the future of their discovery were not farfetched. Since its inception, CRISPR has been experimentally used to address genetic diseases in several models. Scientists have employed CRISPR to modify immune cells in mice to attack tumors, paving the way for future cancer treatments.[4] CRISPR has also been used to modify the mutation that causes sickle cell anemia in mice.[5] Yet another promising application of CRISPR include therapeutic uses in Huntington’s disease, a debilitating neurodegeneration disorder associated with a specific genetic defect.[6] While there are still challenges with applying this technology to disease treatment in humans, progress is being made. The first clinical trial using CRISPR for targeted cancer therapies in the United States was approved by the NIH in June of 2016, and others are now underway.[7]

However, people became concerned when news broke that CRISPR was being used on human embryos. In 2015, a group of scientists in China reported that they had genetically modified human embryos – news that shocked the world and sparked widespread ethical debates.[8] The National Academy of Sciences called upon experts to establish a report of guidelines to outline the restrictions of CRISPR. This set of guidelines did not prohibit the use of CRISPR in humans, provided that such interventions were deemed “safe.”[8] By actively discussing and monitoring the safety and ethics of this technology, we can address the risks while continuing to explore the massive therapeutic potential of CRISPR.

Ironically, Jennifer Doudna admitted to the crowd, “I didn’t set out to cure any disease when I started my career in science.” Yet, her discovery has the therapeutic potential to address cancers, neurological disorders, and more. It was inspiring to learn about Jennifer Doudna’s journey and the way small accumulations of crazy ideas and never-before-tested hypotheses can result in a huge discovery.

Citations

  1. Doudna, Jennifer. “CRISPR Systems: From Adaptive Immunity to Gene Editing.” (2017, Oct 13). William S. Johnson Symposium, Stanford University.
  2. Barrangou, R. (2014, May 16). Cas9 Targeting and the CRISPR Revolution. Retrieved November 03, 2017, from http://science.sciencemag.org/content/344/6185/707.full
  3. CRISPR/Cas9, Genome Editing Tool. (n.d.). Retrieved November 03, 2017, from http://www.origene.com/CRISPR-CAS9/
  4. Robert Sanders, Media relations | April 29, 2016 May 10, 2016, & Sanders, R. (2016, May 10). Doudna named foreign member of UK’s Royal Society. Retrieved November 03, 2017, from http://news.berkeley.edu/story_jump/jennifer-doudna-named-foreign-member-of-uks-royal-society/
  5. September 20, 2017, by NCI Staff, September 11, 2017, by NCI Staff, & August 31, 2017, by Matthew Goetz, M.D. (n.d.). CRISPR Gene-Editing Tool May Help Improve Cancer Immunotherapy. Retrieved November 03, 2017, from https://www.cancer.gov/news-events/cancer-currents-blog/2017/crispr-immunotherapy
  6. “CRISPR deployed to combat sickle-cell anaemia.” (n.d.). Retrieved November 03, 2017, from https://www.nature.com/news/crispr-deployed-to-combat-sickle-cell-anaemia-1.20782
  7. “Can CRISPR Conquer Huntington’s?” (2017, June 29). Retrieved November 03, 2017, from http://blogs.plos.org/dnascience/2017/06/29/can-crispr-conquer-huntingtons/
  8. Sara Reardon. (2016, June 22). “First CRISPR clinical trial gets green light from US panel.” Retrieved November 05, 2017, from https://www.nature.com/news/first-crispr-clinical-trial-gets-green-light-from-us-panel-1.20137
  9. “Chinese scientists genetically modify human embryos.” (n.d.). Retrieved November 03, 2017, from https://www.nature.com/news/chinese-scientists-genetically-modify-human-embryos-1.17378
  10. Achenbach, J. (2017, February 14). “Ethicists advise caution in applying CRISPR gene editing to humans.” Retrieved November 03, 2017, from https://www.washingtonpost.com/news/speaking-of-science/wp/2017/02/14/ethicists-advise-caution-in-applying-crispr-gene-editing-to-humans/?utm_term=.a61c97a70821
Advertisements