GENE EDITING MADE CRISPR

Q: What’s with the missing ‘e’?

A: There isn’t a missing ‘e’. It is how it is spelt. In fact, it is an acronym for Clustered Regularly Interspaced Short Palindromic Repeats.

 

Q: You’ve lost me now, what does all that mean?

A: Guilty as charged. You see it all started with biologists who were studying how bacteria protected themselves against repeated viral attacks. They found that when viruses injected their DNA into bacteria, the bacterial machinery would chop them up into smaller bits and store them in their own genome as clustered short repetitive sequences. These clusters are called CRISPR.
For a long time, nobody clearly knew what these sequences were for. They were attributed different roles such as ensuring that the bacterial genome segregated in equal proportions when bacteria divided. However in 2005 it was first suggested that they might have something to do with providing bacteria with some sort of immunity against viruses.

 

Q: How does the mere storing of viral DNA sequences lead to immunity?

A: The mere storing of the DNA doesn’t automatically confer immunity. It involves the conversion of these DNA sequences into multiple copies of RNA* by a process called ‘transcription’. This process makes sure that the bacteria always retain a ‘hard copy’ of having encountered a viral attack. The RNA molecules are recognised by Cas proteins (CRISPR associated system) in the bacteria and upon encountering a fresh attack, these RNA molecules direct the Cas proteins* to chop up the viral DNA. Essentially, the RNA acts as Google Maps on high accuracy mode to direct the Cas proteins to the right location.

 

*RNA are almost exact copies of DNA differing in being single stranded and containing Uracil nucleotides in place of Thymine that is found in DNA.

crispr.gif

 

Q: Whoa! Never knew that bacteria could do all that. Still don’t understand what the fuss is all about though.

A: The fuss is due to two reasons:

  1. This natural process cuts DNA not only at very specific sites but also does this, regardless of the organism the DNA comes from. This enables researchers to very precisely ‘edit’ DNA in living organisms. Over the last 5 years a large number of eukaryotic organisms have been tested for this including fungi, plants as well as human cells.
  2. This technique is simpler, cheaper and faster than previous techniques (Yes, there were MANY others before). This makes it a technique of choice for companies wanting to edit genomes of plants, fungi and animals for commercial purposes (It’s all about the money, all about the dum dum dara dum dum….). No wonder then that it lead to patent battles.

 

Q: Patent battles? Now it gets exciting. Take me from the top.

A: Right. So the CRISPR-Cas system was first described by Jennifer Doudna (of UC Berkeley) together with Emmanuelle Charpentier (University of Vienna) back in 2012. However, they showed that the technique works in chopping isolated DNA in a tube. By 2013, Feng Zhang, a research at MIT had extended the technique to work in intact eukaryotic cells (i.e plants and human cells).

Armed with this, MIT and Harvard were first to apply for patents for using CRISPR on eukaryotic cells. Sure enough, UC Berkeley and Vienna challenged the patents on basis of ‘interference’ claiming Zheng’s work was incremental to theirs, that is, simply taking the next step on an obvious path that was already lain by researchers at UC Berkeley.

The United States Patents and Trademarks Office (USPTO) in its deliberations came to the decision that Doudna and Charpentier’s findings had no ‘expectation of success’ to work in human cells. For this end, they also relied on a little known magazine quoting Doudna as saying that she had experienced “many frustrations’ and if they could get CRISPR to work in human cells, it would be ‘a profound discovery’.

 

Q: That sounds horrible! Imagine discovering something first and yet not getting the patent for it.

A: It’s true that Doudna and colleagues lost their challenge but the fight is far from over. UC Berkeley has another patent application where they posit CRISPR as a general technique to identify specific DNA sequences in any organism and cut them.

To put it very simply, MIT/Harvard has the patent for blue jeans but UCB is claiming a patent on anything made out of denim.

So if this patent is granted, all biotech companies that want to use CRISPR will have to buy a license from both MIT/Harvard and UCB.

 

Q: Oh boy! Biotech companies will have to shell out more for their research then.

A: Maybe, but only if they decide to use CRISPR exactly the way it was described by Zheng and Doudna. Both Zheng and Doudna have in the meantime discovered alternative system such as the Cpf1 and CasX/CasY that are distinct from the ones before. This means companies can use these new techniques instead and get away from any unnecessary patent buying.

Also, we have barely found a handful of DNA editing methods. In the future, someone might stumble across an even better method of editing DNA and CRISPR will be left on the wayside.

 

Q: So what does all this mean for me? Is all my food going to be “Crispr”-ed?

A: Not so fast bunny rabbit! Science communication is hard work and you could show us some love by following us on twitter @IndSciComm or telling others about us.

Watch this space for more about how CRISPR might change your life without your knowledge.

References

1.Jinek, M. et al. Science 337, 816–821 (2012)

2. Cong, L. et al. Science 339, 819–823 (2013)

3.http://www.nature.com/news/why-the-crispr-patent-verdict-isn-t-the-end-of-the-story-1.21510

4.https://www.technologyreview.com/s/603662/patent-office-hands-win-in-crispr-battle-to-broad-institute/

5.https://www.washingtonpost.com/news/speaking-of-science/wp-content/uploads/sites/36/2017/02/DecisionsOnMotions.pdf

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