Much has been made about the promise and perils of gene editing and CRISPR Cas9 technology.  The Center for Individualized Medicine’s Kristin Clift offers an introduction to this powerful gene editing tool that holds the potential of allowing scientists to modify DNA with extreme precision.

By Kristin Clift

Imagine you’re a patient and your doctor just delivered some bad news to you. You have a BRCA mutation causing significant increase in the risk of breast and ovarian cancer, but wait, there is a treatment that can replace the faulty genetic code with one that isn’t harmful. This scenario may seem like science fiction, but it’s a lot closer to becoming a reality.

You may or may not have heard about the genome editing technology, CRISPR Cas9 in the news lately. Genome editing isn’t exactly a new technology, what’s new about it is how it’s done and how it’s improving. There are gene editing methods that have been in use for a while such as TALEN (Transcription activator-like effector nucleases), but CRISPR Cas9 is the most popular and sensationalized technique that everyone is talking about. So here’s the scoop:

Overview
Oftentimes people describe our genome using the analogy that it is like a cookbook. Each recipe is a gene. This cookbook has ~20,000 recipes in it that make up the awesome feast that is your body. So to conceptualize what genome editing is, imagine you are typing out this cookbook of life. If our genome is a bunch of recipes that provides instructions on how to make our bodies, then genome editing or engineering is a technique that is similar to using the “find and replace” function on a word process0r. Say you’re typing out a cake recipe and you decide to switch out baking soda for baking powder . . . find and replace. That’s an over-simplified analogy but that’s what I can wrap my head around.

CRISPR is short for “Clustered regularly-interspaced short palindromic repeats,” a phenomenon that scientists in the yogurt industry noticed in bacteria. CRISPR is a form of acquired immunity that bacteria use as a defense mechanism against viruses. It takes a snapshot of the virus’ DNA and inserts it into its own sequence so that it will know how to fight it if it ever comes across it again.

The CAS9 stands for CRISPR Associated Protein 9, which could be described as scissors with a built in GPS, or again to tie it to the original analogy the find and replace (or insert) mechanism in a word processor. Scientists have figured out how to harness the methods of CRISPR CAS9 to find, cut, and insert changes into genomes.

Potential
The important thing being, with this technique we may be able to edit serious genetic diseases (i.e., Huntington’s Disease, Tay Sachs, etc.) out of the human genome.

Furthermore, scientists are working on editing out HIV from human cell lines and researchers in China have recently inserted HIV resistance into human embryos. There are endless possibilities. So why aren’t we solving all the world’s problems with this technology right now?

Whoa, There
Imagine you’re the patient again, and you want to make sure your future children don’t carry the same harmful BRCA mutation that runs in your family . . . so you take the embryos you’ve produced and they use CRISPR to edit that gene . . . and then you decide while they’re at it, could they make the baby super tall and have green eyes, too (the movie Gattaca anyone?).

If you let your science fiction imagination run wild for a minute, you could imagine all the crazy things that we could end up doing with this technology. For instance, we could turn chickens into dinosaurs. In real life right now, you can buy a CRISPR-ized mini pig for a pet for $1,500 from China.

The U.S. Director of National Intelligence James Clapper added genome editing to the list of the 6 Weapons of Mass Destruction — implying that it could be used in extremely nefarious ways such as the creation of a new deadly virus, or like in the new X-Files episode, it could be used to strip people of their immune systems (essentially giving everyone the Bubble Boy syndrome).

So, yes, you can imagine there are a lot of concerns over this technology. Scientists have requested a “moratorium” meaning they want to put using it on hold until we think through all of the possible implications (i.e., how it will effect evolution, extinction, will people use it for embryo modification to make "designer babies," etc. There are many things we need to consider before going in that direction, like How will people currently living with disabilities perceive it? ).

As with any new technology, there are limitless possibilities that it can be used for both good and bad (for instance, cars, Internet, smartphones, etc.). But the potential for good is so monumental that we need to move quickly and take as many steps as possible to try to diminish its harmful potential.

How Will It Be Used in the Clinic in the Near Future?
I spoke with Paldeep Atwal, M.B., Ch.B., medical director of Clinical Genomics at Mayo Clinic Florida. Dr. Atwal says the main problem right now with genome editing is the off target-effects. Using the find and replace analogy again, it’d be like if you wanted to replace the word “and” with “or,” which is easily done, but it could accidentally change the word “band” to “bor” if you’re not careful. Which is bad if you’re turning in an important report, but really bad if you’re editing the code of life. However, the technology is continuously improving and scientists are constantly working on ways to minimize the off-target effects. Until all effects are known or eliminated, it may be awhile before we see its use in the clinic.

Meanwhile, in a research setting, there are other uses for CRISPR that will revolutionize the way we understand genomics. Basically, scientists can blunt the scissors to do research on how genomes work. Using CRISPR in functional genomics is another way researchers can learn more about genomics and human health.

Summary
CRISPR is an extraordinary new technique that is cheaper and easier to use than previous technologies. In the future, our genetic code may not be written in stone. A BRCA mutation can be remedied and your chances getting of breast or ovarian cancer would be drastically reduced. Diseases that mutate our genes such as cancer could be rewritten. We will be able to hardwire resistance to viral diseases to our cells. We can extend the life of children born with Tay-Sachs or other terminal genetic diseases. These miraculous uses of CRISPR may come sooner than we think, but not without great care and thought.

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Kristin Clift has a background in medical anthropology. After a three-year stint with the biomedical ethics group at Mayo Clinic in Rochester, Minnesota, she is currently supporting research and education efforts for the Center for Individualized Medicine at Mayo Clinic Florida.

 

 

 

So Much to Read, So Little Time
If you want to find out more about gene editing, here are some great links to help you understand more about the promise and perils of CRISPR/Cas9 and gene editing technology.

“Arguments for and against Editing Human Embryos - Business Insider.” Accessed February 16, 2016. http://www.businessinsider.com/arguments-for-and-against-editing-human-embryos-2015-12.

Bessen, Jeff. “CRISPR/Cas Gene-Editing Technique Holds Great Promise, but Research Moratorium Makes Sense Pending Further Study.” The Conversation. Accessed February 16, 2016. http://theconversation.com/crispr-cas-gene-editing-technique-holds-great-promise-but-research-moratorium-makes-sense-pending-further-study-43371.

“California Stem Cell Agency May Fund Tests to Edit Genes in Human Embryos - LA Times.” Accessed February 16, 2016. http://www.latimes.com/business/la-fi-human-gene-editing-20160212-story.html.

Callaway, Ewen. “UK Scientists Gain Licence to Edit Genes in Human Embryos.” Nature 530, no. 7588 (February 1, 2016): 18–18. doi:10.1038/nature.2016.19270.

Carl Zimmer, Quanta Magazine, 2015 Feb. 18, 125 343, and 43. “The Biggest Biotech Discovery of the Century Is about to Change Medicine Forever.” Business Insider. Accessed February 16, 2016. http://www.businessinsider.com/the-biggest-biotech-discovery-of-the-century-is-about-to-change-medicine-forever-2015-2.

“CRISPR’s Most Exciting Uses Have Nothing to Do With Gene-Editing - The Atlantic.” Accessed February 16, 2016. http://www.theatlantic.com/science/archive/2016/01/the-most-exciting-uses-of-gene-editing-technology-involve-no-editing/422619/.

“CRISPR: The Good, the Bad and the Unknown : Nature News & Comment.” Accessed February 16, 2016. http://www.nature.com/news/crispr-1.17547.

“DNA is a recipe, NOT a blueprint.” https://beagleandbeyond.wordpress.com/2011/10/16/dna-is-a-recipe-not-a-blueprint/

“Focus on: Gene Editing.” Accessed February 16, 2016. http://thebiologist.rsb.org.uk/biologist-features/158-biologist/features/1441-focus-on-gene-editing.

“Gene Editing Tool Used to Treat Girl’s Cancer in Medical First.” STAT, November 5, 2015. http://www.statnews.com/2015/11/05/doctors-report-first-use-gene-editing-technology-patient/.

“Improving CRISPR’s Cut and Paste Function | GEN News Highlights.” GEN. Accessed February 16, 2016. http://www.genengnews.com/gen-news-highlights/improving-crispr-s-cut-and-paste-function/81252269/.

Ledford, Heidi. “CRISPR, the Disruptor.” Nature 522, no. 7554 (June 3, 2015): 20–24. doi:10.1038/522020a.

“Multiplex Genome Engineering Using CRISPR/Cas Systems” L. Cong et al. Science 339, 819–823; 2013

Odling-Smee, Lucy, Heidi Ledford, and Sara Reardon. “Genome Editing: 7 Facts about a Revolutionary Technology.” Nature, November 30, 2015. doi:10.1038/nature.2015.18869.

“A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity.” M. Jinek et al. Science 337, 816–821; 2012

“The Public and Genetic Editing, Testing, and Therapy.” https://cdn1.sph.harvard.edu/wp-content/uploads/sites/94/2016/01/STAT-Harvard-Poll-Jan-2016-Genetic-Technology.pdf

“Top U.S. Intelligence Official Calls Gene Editing a WMD Threat.” MIT Technology Review. Accessed February 16, 2016. https://www.technologyreview.com/s/600774/top-us-intelligence-official-calls-gene-editing-a-wmd-threat/.

Yong, Ed. “Clinical Genetics Has a Big Problem That’s Affecting People’s Lives.” The Atlantic, December 16, 2015. http://www.theatlantic.com/science/archive/2015/12/why-human-genetics-research-is-full-of-costly-mistakes/420693/.

———. “The New Gene-Editing Technique That Reveals Cancer’s Weaknesses.” The Atlantic, November 25, 2015. http://www.theatlantic.com/science/archive/2015/11/a-revolutionary-gene-editing-technique-reveals-cancers-weaknesses/417495/.

———. “The Quest to Make CRISPR Even More Precise.” The Atlantic, December 1, 2015. http://www.theatlantic.com/science/archive/2015/12/who-edits-the-gene-editors/418209/.

CRISPR, the disruptor Nature | June 3

 Everything You Need to Know About CRISPR, the New Tool that Edits DNA

The Genome Engineering Revolution Tech Crunch | May 13

 UK scientists reject call for moratorium on gene editing BMJ | May 13

 Embryo engineering a moral duty, says top scientist BBC | May 13

 A prudent path forward for genomic engineering and germline gene modification Science | April 3

Genome editing poses ethical problems that we cannot ignore The Conversation | March 31

 Let's Hit 'Pause' Before Altering Humankind WSJ | April 8

 Engineering the Perfect Baby MIT | March 5

 Scientists Seek Ban on Method of Editing the Human Genome NYT | March 19

 Don’t edit the human germ line Nature | March 12

CRISPR germline engineering—the community speaks  Nature Biotechnology | May 12

 

 

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