title.png

 

 

 
crispr-comic-1.jpg
 

 

Clustered Regularly Interspaced Short Palindormic Repeats - CRISPR - is a family of DNA that exists within bacteria for the purpose of protecting them from harmful viruses. Essentially, it is the immune system of bacteria. However, when you see CRISPR in the news or hear about it from your annoyingly smart friend, it refers to scientists using that same system to edit the DNA of organisms. To take a step back for a second, let's think about what this means. DNA is the microscopic material that defines the traits of all organisms, ranging from tomatoes to mosquitoes to dogs to humans.

 
chart.png
 

Imagine being able to edit the very DNA that causes the above traits, and then imagine the far-reaching impacts of society having that ability. This is what CRISPR gene editing can do and is what is currently being researched in labs all over the world.

 

How does CRISPR work?

To explore how scientists can use CRISPR, we first need to understand how bacteria use CRISPR to defend against viruses. Let's create a scene.

 
Photo Apr 03, 12 12 53 PM.png
 

Bethany is a bacterium, floating along and minding her own business. Vince, a destructive virus, comes along and starts attacking Bethany. Putting up a good fight, Bethany is able to fend off Vince. After she successfully incapacitates him, she decides to protect herself from Vince in case they cross paths in the future. She pulls out her camera and snaps a photo of her attacker. Next time she brushes by some unknown viruses, she'll whip out the picture to see if Vince is there. If she does happen to see Vince again, she'll have the upper hand and be prepared to easily fend him off.

Bethany's photograph - a reference to danger - is what CRISPR is. When a bacterium survives a viral attack, the bacterium actually saves bits of the virus's DNA within its own DNA. This acts as an immune response. In the future, the bacterium can more easily defend against similar viral attacks.

Scientists first became intrigued by this process in 2005, when they realized the implications of a bacterium being able to snip their own DNA and add in pieces of brand new DNA. If they could replicate this, it could mean more nutritious and longer lasting produce, mosquitos that don't carry disease, and even a human gene-pool devoid of genetic diseases.

Since 2005, researchers have broken down the individual elements that make CRISPR possible, and have created a process that allows them to recreate CRISPR in the lab. The first element is an enzyme called Cas9. Cas9 is the tool that actually cuts the DNA in preparation for adding in new genetic material. The second is a guide RNA. The gRNA acts as a DNA search function to find the desired location for the new genetic code to be added. The last element is the repair template, which is the new DNA sequence to be inserted into the site of the Cas9-broken DNA. Put simply, the process is as follows:

 
grna-dna.jpg
 
 

gRNA searches for the location within the DNA where the new code should be inserted

 
 
cas9-dna.jpg
 
 

Cas9 snips the DNA at the identified location

 
 
dna.jpg
 
 

The cell repairs itself, and in the process inserts new DNA from the repair template

 

 

 

What is the current status of CRISPR?

CRISPR technology is moving forward at a breakneck speed. Proving to be truly revolutionary, there are far more successfully attempted applications than could be concisely added to this article. Here are a selection of applications that are truly exciting:

  • A test called DETECTR that detects instances of HPV within cells and then releases a fluorescent indicator showing a positive result. The tests takes an hour and costs less than a dollar to perform.
  • A tool called SHERLOCK can identify if Zika or dengue are present in a sample of blood. The tests come in the form of strips and are faster and more sensitive than current tests.
  • A team at Harvard showed how CRISPR can be used to track what has happened in a cell. This can be used to record which chemicals a certain cell is coming into contact with.
  • The company eGenesis has been removing viral DNA from pig organs, which would make them viable options for transplants in humans.
  • A team at Harvard have claimed to be a year away from being able to create an embryo indistinguishable from that of a woolly mammoth - a creature than went extinct over 4000 years ago.
  • Researchers at the Gladstones Institute have used CRISPR to convert skin cells from mice into stem cells. This technique could be an extremely inexpensive way to create the highly sought-after type of cell.
  • Chinese researchers have used CRISPR to edit genes in pigs to reduce the amount of fat they carry by 24%. Not only does this produce healthier bacon, but it also reduces costs to farmers by allowing the pigs to more effectively regulate their body temperature.

 

What is the immediate future of CRISPR?

Companies seeking to capitalize on the revolutionary CRISPR technology have been flooding the market over the last few years. This has led to the industry moving at a break-neck speed to be among the first to bring CRISPR to consumers. While we are still a few years away from you knowing someone who has been treated with CRISPR, 2018 will mark the year where clinical trials begin in the US and Europe:

  • CRISPR Therapeutics is set to begin a clinical trial that aims to cure the disease beta thalassemia by using CRISPR to implement a genetic correction to patients' blood cells.
  • Editas Medicine had planned to begin a trial in 2017 that would use CRISPR in an attempt to cure a rare form of blindness. This trial was delayed, but is set to begin this year.
  • Intellia Therapeutics began clinical trials on monkeys in 2017, and plans to use those results to apply for human trials. They are currently in preclinical development for numerous procedures, including therapies for Hepatitis B in addition to 3 genetic diseases.
  • Researchers at Stanford University School of Medicine are planning to apply for clinical trials of a treatment for sickle cell disease.

 

Expert Forecast

To get some thoughts from an industry expert on CRISPR, I reached out to Kevin Doxzen, who works as the Science Communications Specialist at the Innovative Genomics Institute. Kevin received his PhD from UC Berkeley, where he studied under Jennifer Doudna. Dr. Doudna is lauded as a leading figure of the "CRISPR revolution" that has occurred in the last few years, and is often credited as the first person to take CRISPR from a bacterial immune system to a gene editing technology.

How long do you think it will be before we see applications involving CRISPR available to consumers/patients?

2018 will mark the beginning of clinical trials using CRISPR genome editing technology. Clinical trials last for multiple years and once safety and efficacy have been shown, CRISPR therapy will be available to the public.. Thus, the technology may be ready for patients in only a few years.

What do you think those first applications will be?

I think the first applications using CRISPR to treat physical ailments will focus on Sickle Cell Disease, Cancer, Muscular Dystrophy, and Blindness. Beyond biomedicine, CRISPR will have a more pronounced and immediate impact in the agricultural world. You will see many more CRISPR edited crops in farm fields before you see a list of CRISPR therapies in a doctor's office.

What might the technology look like in 10-15 years?

In 10-15 years I think CRISPR will definitely be an option for patients to treat several rare genetic diseases and will probably be an option to treat more common diseases such as Huntington's Disease. I think organisms that have been edited using CRISPR will have been deployed into the wild. Examples of this may include edited bacteria to help save coral reefs from extinction, edited mosquitos to help save birds from avian malaria, and edited rodents to stop the spread of invasive species. Lastly, I think that the number of GMO products will significantly increase and become more widespread in American culture.

In what significant ways do you think our everyday lives will be improved because of technology related to CRISPR?

I hope that using CRISPR to edit plants will help put food on the table for more families, lower costs, and help agriculture survive in a changing climate. I also think that some diseases which take the lives of babies or small children will now become treatable. I also think that diseases which are rare and which don't gain attention from pharmaceutical companies will now be given a treatment option.
Today, young middle schoolers can go into their bedrooms and code a new phone app or design software for a robot. I think in 15 years, interested members of the public will be able to go to DIY biology centers in their city and perform interesting and possibly beneficial gene editing experiments. There has been a lot of hype around the DIY CRISPR community, but despite what people think, CRISPR cannot be used to edit any organism in the comfort of someone's home. Rules and regulations need to be put in place now, but under the supervision and support of local DIY facilities, people might be able to design bacteria to produce life-saving molecules or edit crops that can withstand drought.

Besides CRISPR gene editing, what bleeding-edge technology are you most excited about?

I think CRISPR and Artificial Intelligence will join forces for certain purposes. People are using AI to scan and decipher genomes, which could help make CRISPR more precise and efficient at editing DNA. I think the 2000's and 2010's have been about the human genome, but I think the 2020's will be about the brain. Researchers are going to make significant strides in our understanding of the brain, which will have enormous implications on society. I think it's tough to predict these exact implications, but they will surely be significant.
 
 
 
 
crispr-comic-2.jpg