The discovery of CRISPR genome editing technology in 2012 has turned genome editing from a time-consuming and arduous task into a simple matter of cut-and-paste. Researchers can now edit the genomes of living organisms with incredible precision, which has made a huge impact across the field of biology and medicine.
What is genome editing?
Humans have been manipulating the genes of living things for tens of thousands of years. Through selective breeding over many generations, we influenced the genetics of wolves to become more like modern day dogs. We also selectively bred crops, so that genes leading to higher yields and tastier foods became more prevalent each year.
It wasn’t until the last few decades that we’ve developed tools to edit genes directly, as opposed to the more passive method of selective breeding, but many of these are still time-consuming and inefficient.
That all changed with the development of the CRISPR technique in 2012 by Jennifer Doudna and Emmanuelle Charpentier who were awarded the Nobel Prize in Chemistry for their achievement eight years later. “You can do the same sorts of things as with previous genome editing techniques, but much faster, much cheaper, and much more efficiently,” explains Robin Lovell-Badge, head of the Developmental and Stem Cell Biology Lab at the Crick. “It’s also more flexible; you can change pretty much anything you want.”
What is CRISPR?
CRISPR is shorthand for a process that was first discovered occurring naturally in bacteria – it stands for “clustered regularly interspaced short palindromic repeats." The researchers that discovered the technique realised that they could copy the process and use it on any kind of cell.
Christophe Galichet, a senior laboratory research scientist in Robin’s lab, describes the two fundamental elements of the genome editing process. “You have a piece of genetic material called guide RNA, which acts as a sort of postcode that’s used to find the exact spot on the DNA you want to cut, and the CAS9 enzyme, which acts as a pair of scissors that do the cutting.”
From there, the cell’s existing repair mechanisms will kick in to try and repair the newly-broken DNA, but scientists can manipulate the repair process to change, add or remove specific pieces of a genome. This basic toolset can be built upon to edit specific pieces of DNA in any way a researcher might need.
In just the last few years, the process has already become so well-established that a researcher can order the exact CRISPR components they need from a specialised lab, run hundreds of different tests at a time, and generate their results in as little as two weeks.
Honing the technique
Although CRISPR was a huge improvement on previous genome editing techniques, as with any new technology there were still some kinks to iron out. Paola Scaffidi, who leads the Crick’s Cancer Epigenetics Lab, recalls an email she received late one evening in 2018 that simply read “I found it!” while her team was working on one of these obstacles.
The message came from Tristan Henser-Brownhill, a student in Paola’s lab at the time. He’d discovered a relatively simple set of rules that predicted how accurate a CRISPR edit would be depending on what the “postcode” of the guide RNA looked like. This finding has made it easier for researchers to design cuts that are more efficient and less prone to errors.
CRISPR at the Crick
Robin’s lab uses CRISPR in a number of experiments, particularly in their recent projects looking at how an organism’s sex is determined. They use a straightforward screening technique which involves “knocking out” one section of DNA at a time and seeing whether it has any impact on the process being studied, in this case sex determination.
Using this method, Robin’s team discovered a section of DNA that was unexpectedly crucial in determining the sex of a mouse. When the section of DNA was inactivated, it caused the mice to develop as female, even when they contained the typically male pairing of XY chromosomes.
The scientists in Robin’s team aren’t the only ones who have adopted the use of CRISPR in their research. In a review conducted in 2020, Christophe found that around 80% of labs at the Crick incorporated the genome editing technique at some point in their research. It helped Crick researchers identify the genes involved in SARS-CoV-2 replication, is used in a number of cancer studies, and scientists continue to develop new ways of applying CRISPR to their experiments.
The future of genome editing
Despite improvements on the techniques from labs like Paola’s, CRISPR still isn’t perfect, which is why experiments and treatments that incorporate genome editing are designed to account for and overcome any unintended consequences. More research is needed to understand the current limitations of CRISPR and how the technique might be further improved.
CRISPR is already being used in trials to treat human diseases, such as sickle cell anemia, and it’s not hard to imagine the many ways it could be applied to humans in the future. It’s a topic that requires serious thought about how far the technology should be taken, but there’s no doubt that it’s already had a massive positive impact across the fields of biological and medical research.