Explainer: CRISPR

Willow Beck
Quinn Emmett
October 27, 2022
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What is CRISPR CAS9

Despite the catchy acronym, CRISPR has nothing to do with making your DNA crunchy (yet). Obviously, the term stands for Clustered Regularly Interspaced Short Palindromic Repeats. Rolls right off the tongue.

You may have read controversial headlines about this new technology - but what is it? Is CRISPR a miracle disease stopper, or are scientists flying too close to the sun? Those questions are still being asked and considered by people much smarter than me, so for now, let’s focus on the fries and gravy of the science itself.

CRISPR Cas9 is a gene editing technology that works by targeting and altering a specific piece of DNA. The technique will potentially revolutionize genetic biology, as it is faster, cheaper, and more accurate than previous techniques, with a wide range of potential applications.

How does CRISPR work

The “explain it to me like I’m five” version is that CRISPR Cas9 is arts and crafts at the DNA level. The process involves a small piece (about 20 bases long) of a pre-designed RNA sequence (called guide RNA or gRNA) located within a longer RNA scaffold. This scaffold binds to the piece of DNA intended for editing and guides an enzyme called Cas9 to the intended part of the genome. Cas9 cuts two strands of DNA at that specific location so other bits of DNA can be added or removed. When the cut is made, scientists intervene using DNA repair machinery to introduce a mutation (a new base sequence).

History of CRISPR

Since we discovered DNA and genes, scientists have been studying the effects of changes to DNA as the best way to understand gene function. Before scientists could introduce a mutation manually, this was historically done using chemicals or radiation, and there was no control over where a mutation would occur in the genome.

Other types of gene targeting that introduce changes to specific places in the genome by removing or adding whole genes or single bases take a long time and are expensive.

Who discovered CRISPR

Say it with me: science is a process, building on the work of many people. The history and development of CRISPR can be attributed to multiple scientists over many decades...not to mention the bacteria that figured it out millions of years ago.

In the late 1980s, Japanese student Yoshizumi Ishino discovered repeating sections of 28 base pairs in the DNA of E. coli bacteria but did not determine their biological significance. In the 1990s, Spanish student Fanscisco Mojica determined these sequences are a built-in gene editing system used by bacteria to respond to invading pathogens (basically, bacteria’s version of an immune system).

Cut to 2011. Jennifer Doudna at the University of California, Berkeley teamed up with Emmanuelle Charpentier at the University of Vienna to investigate a particular CRISPR-associated enzyme called Cas9 and figured out how it works with gRNA. From there, they determined that they could program Cas9 with a single piece of RNA and direct the complex to cut double-stranded DNA at a specific sequence - adapting the bacterial system to be used in other cells. While several other scientists around the world were discovering something similar at around the same time, resulting in a patent war over the technology, Doudna and Charpentier were credited for their work by receiving the 2020 Nobel Prize in Chemistry, becoming the first women to win without sharing the award with a man.

What is CRISPR used for

The ability to readily and cheaply edit genes has many applications from health care to agriculture. The benefits of CRISPR include treating medical conditions with a genetic component from single-gene disorders like cystic fibrosis, hemophilia, and sickle cell disease to more complex diseases like cancer, heart disease, and mental illness.

Is CRISPR safe for humans?

The safety of CRISPR for humans is still being tested, and there are a lot of wrinkles that still need to be smoothed out. For example, not all of the gRNA bases need to match the target sequence for the gRNA to bind, resulting in “off-target” effects. Even if 19 of the 20 complementary bases exist somewhere different in the genome, and the gRNA bind there instead causing the Cas9 enzyme to cut at the wrong site and introduce a mutation in the wrong location, the potential effects on the cell function could be catestrophic. Most CRISPR research is currently focused on off-target effects, and clinical trials using CRISPR are currently underway, including trials using CRISPR as a cancer therapy.

CRISPR CAS9 ethical issues

Most applications of CRISPR involve editing somatic (non-reproductive) cells that aren’t passed down to offspring. There is debate about the potential to edit reproductive cells, causing changes to be passed on from generation to generation. There are ethical implications to this kind of application, including "CRISPR babies" and racist and ableist assumptions.

CRISPR regulations

Gene editing in reproductive cells is currently illegal in most countries, at least in cells that will result in pregnancy. Recommendations on the future of clinical applications of human germline genome editing using CRISPR state that the research should not proceed unless:

  • “There is a compelling medical rationale
  • an evidence base that supports its clinical use
  • an ethical justification
  • a transparent public process to solicit and incorporate stakeholder input”

The future of gene editing is exciting and uncertain, with the potential to save many lives but also cause irreparable damage. As Jennifer Doudna puts it:

“The power to control our species’ genetic future is awesome and terrifying. Deciding how to handle it may be the biggest challenge we have ever faced.”

Go deeper into genetics

Episode 51 - What the hell is CRISPR? with Brandon Ogbunu

Episode 129 - Indigenous DNA with Krystal Tsosie

Sources

https://www.newscientist.com/definition/what-is-crispr/

https://www.yourgenome.org/facts/what-is-crispr-cas9/

https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/

https://geneticsunzipped.com/transcripts/2021/4/8/hello-crispr

https://www.synthego.com/learn/crispr

https://www.discovermagazine.com/health/crispr-gene-editing-technology-enters-the-body-and-space


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