What is CRISPR?

CRISPR. What is it? And why is the scientific community so fascinated by its potential applications? We explain how this technology harnesses an ancient bacteria-based defense system — and how it will impact the world around us today.

CB Insights
Feb 16, 2018 · 8 min read

This piece is excerpted from a long-form overview of CRISPR and its potential impact. See the full analysis on our Research Portal.

Imagine a future where parents can create bespoke babies, selecting the height and eye color of their yet unborn children. In fact, all traits can be customized to one’s preferences: the size of domestic pets, the longevity of plants, etc.

It sounds like the backdrop of a dystopian science fiction novel. Yet some of this is already happening.

Since its initial discovery in 2012, scientists have marveled at the applications of CRISPR (also known as Cas9 or CRISPR-Cas9).

And with a Jennifer Lopez-produced bio-terror TV drama called C.R.I.S.P.R. on the horizon, CRISPR has reached a new peak in interest from outside the scientific community.

CRISPR may revolutionize how we tackle some of the world’s biggest problems, like cancer, food shortages, and organ transplant needs. Recent reports even examine its use as a highly efficient disease diagnostics tool. But, as with any new technology, it may also cause new unintended problems.

Changing DNA — the code of life — will inevitably come with a host of important consequences. But society and industry can’t have this conversation without understanding the basics of CRISPR.

In this explainer, we dive into CRISPR, from a simple explanation of what exactly it is to its applications and limitations.

What is CRISPR?

CRISPR is a defining feature of the bacterial genetic code and its immune system, functioning as a defense system that bacteria use to protect themselves against attacks from viruses. It’s also used by organisms in the Archaea kingdom (single-celled microorganisms).

The acronym “CRISPR” stands for Clustered Regularly Interspaced Short Palindromic Repeats. Essentially, it is a series of short repeating DNA sequences with “spacers” sitting in between them.

In short, bacteria use these genetic sequences to “remember” each specific virus that attacks them.

They do this by incorporating the virus’ DNA into their own bacterial genome. This viral DNA ends up as the spacers in the CRISPR sequence. This method then gives the bacteria protection or immunity when a specific virus tries to attack again.

Accompanying CRISPR are genes that are always located nearby, called Cas (CRISPR-associated) genes.

Once activated, these genes make special proteins known as enzymes that seem to have co-evolved with CRISPR. The significance of these Cas enzymes is their ability to act as “molecular scissors” that can cut into DNA.

Image: Generalized CRISPR locus. Credit: Lee S, et al. Journal of Cellular Biotechnology

In harnessing this technology, researchers have added a new step: after DNA is cut by CRISPR-Cas9, a new DNA sequence carrying a “fixed” version of a gene can nestle into the new space. Alternatively, the cut can altogether “knock out” of a particular unwanted gene — for example, a gene that causes diseases.

How it works

These are the 3 key players that help the CRISPR-Cas9 tech do its work:

  1. Guide RNA: a piece of RNA (a genetic cousin of DNA) that locates the targeted gene. This is engineered in a lab.
  2. CRISPR-associated protein 9 (Cas9): the “scissors” that snip the undesired DNA out
  3. DNA: the desired piece of DNA that is inserted after the break

Below, we illustrate how these parts come together to create a potential therapy.

The guide RNA serves as the “GPS coordinates” for finding the piece of DNA you want to edit and zeroes in on the targeted part of the gene. Once located, Cas9, the scissors, makes a double stranded break in the DNA, and the DNA you want to insert takes its place.

Applications of CRISPR

Every industry can harness CRISPR as a tool: it can create new drug therapies for human diseases, help farmers grow pathogen-resistant crops, create new species of plants and animals — and maybe even bring back old ones.

Animal-related research

Though still in early stages, “animal models” (i.e. lab animals) have provided key insights into how we may be able to manipulate CRISPR.

Mice have been especially telling when it comes to CRISPR’s therapeutic potential. As mammals sharing more than 90% of our human genes, mice have been used as ideal test subjects.

Experiments on mice have shown that CRISPR can disable a defective gene associated with Duchenne muscular dystrophy (DMD), inhibit the formation of deadly proteins involved in Huntington’s disease, and eliminate HIV infection.

Other CRISPR animal trials have ranged from genetically engineering long-haired goats for higher production of cashmere to breeding hornless cows to avoid the painful process of shearing horns off.

Human-related research

Compared to research involving animals, CRISPR trials that edit human DNA have moved more slowly, largely due to the ethical and regulatory issues at play.

Given the permanent nature of altering a human’s genome, the FDA is approaching CRISPR cautiously. Some scientists have even proposed a moratorium on CRISPR trials until we have more information on the potential impact on humans.

Affected industries

Pharmaceuticals & biotechnology

The future of medicine will be written with CRISPR.

The current drug discovery process is long, given the need to ensure patient safety and gain a thorough understanding of unintended effects. Moreover, current US regulatory policies often result in a decades-long development process.

However, teams using CRISPR can bring customized therapies to market more quickly than was previously dreamed, speeding up the traditional drug discovery process.

Timeline of drug development. Credit: PhRMA

CRISPR’s cheap price tag and flexibility allows accurate and fast identification of potential gene targets for efficient pre-clinical testing. Because it can be used to “knock out” different genes, CRISPR gives researchers a faster and more affordable way to study hundreds of thousands of genes to see which ones are affected by a particular disease.

Of course, along with providing a more streamlined drug development process, CRISPR offers the possibility of new ways to treat patients.

For example, monogenic diseases — diseases caused by a mutation in a single gene — present an attractive starting point for CRISPR trials. The nature of these illnesses provides an exact target for the treatment: the problematic mutation on a single gene.

Blood-based, single-gene diseases like beta-thalassemia or sickle cell are also great candidates for CRISPR therapy, because of their ability to be treated outside of the body (known as ex-vivo therapy). A patient’s blood cells can be taken out, treated with the CRISPR system, then put back into the body.

Food & agriculture

An early application of CRISPR was pioneered by yogurt company Danisco in the 2000s, when scientists used an early version of CRISPR to combat a key bacterium found in milk and yogurt cultures (streptococcus thermophilus) that kept getting infected by viruses. At that point, the ins and outs of CRISPR were still unclear.

Fast forward to today, when climate change will further increase the need to use CRISPR to protect the food and agriculture industries against new bacteria. For example, cacao is becoming difficult to farm as growing regions get hotter and drier. This environmental change will further exacerbate the damage done by pathogens.

To combat this issue, the Innovative Genomics Institute (IGI) at UC Berkeley is applying CRISPR to create disease-resistant cacao. Leading chocolate supplier MARS Inc. is supporting this effort.

Gene editing can make farming more efficient. It can curb global food shortages for staple crops like potatoes and tomatoes. And it can create resilient crops, impervious to droughts and other environmental impacts.

Regulators have shown little resistance to gene-edited crops, and the United States Department of Agriculture (USDA) in particular is not regulating the space. This is largely because when CRISPR is applied to crops, there’s no foreign DNA being added: CRISPR is simply used to edit a crop’s own genetics to select for desirable traits.

In 2016, the white button mushroom, modified to be resistant to browning, became the first CRISPR-edited organism to bypass USDA. In October 2017, it was announced that agriculture company DuPont Pioneer and the Broad Institute would collaborate for agriculture research using their CRISPR-Cas9 intellectual property.

In January, biotech company Yield10 Bioscience got approval for its CRISPR-edited plant Camelina sativa (false flax), which has enhanced omega-3 oil and is used to make vegetable oil and animal feed.

These are indications that new breeds of crops could reach markets much faster than previously thought. Without USDA oversight, these items and other food products could go into production relatively quickly.

This will impact the food we eat, as food items are edited to carry more nutrients or to last longer on grocery shelves.

Another area currently generating buzz is the production of leaner livestock.

In October 2017, scientists at the Chinese Academy of Sciences in Beijing used CRISPR to genetically engineer pig meat that had 24% less body fat.

Image: Infrared pictures of 6-month-old pigs at zero, two, four hours after cold exposure. Gene edited pigs are on the right side of the images. Credit: Zheng et al./PNAS

Researchers did this by inserting a mouse gene into pig cells in order to better regulate body temperature. Although this example technically makes the result a GMO product, it may not be too long before pigs’ genes are used for the same purpose.

Future versions of this technology applied to human nutrition will be one area to look out for.

Closing Remarks

The landscape of gene editing could look completely different in 100, 50, or even 10 years.

In the future, it might be standard to tweak or design genes in plants, animals, and even human beings, irrevocably affecting the gene pool and the course of evolution.

While some ideas presented above may seem far-fetched at this the moment, that could easily change. After all, CRISPR isn’t an expensive, inaccessible form of technology. It’s available and in use now. From farmers to researchers, CRISPR will make its impact in our society.

CB Insights

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