What is CRISPR and how is it changing the face of gene editing?
Can you imagine being able to quickly and cheaply edit genes to regulate blood glucose levels without insulin injections, reduce the population of disease-causing insects, cure diseases like sickle cell anaemia and cystic fibrosis, or give plants resistance to disease without using chemicals?
Although not yet a reality, these innovations and many more could be just around the corner, thanks to a technique called Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR). So, what is CRISPR and how is it changing the face of gene editing?
What is CRISPR?
CRISPR technology is based on the way that bacteria defend themselves against viruses. If a bacterium survives a virus attack, it copies pieces of the virus’ DNA and incorporates these into its own genomes. These copies are used like mug shots to allow the bacteria to identify harmful viruses.
To keep track of this collection of “mug shots” and to keep them separate from the bacteria’s own DNA, the bacteria place repetitive sequences of molecules around each one. When a bacterium comes up against a harmful virus with a genetic “mug shot” in its collection, it sends an enzyme to cut apart and destroy anything that matches it.
Once scientists figured out how bacteria do this, they were able to use a similar approach to easily cut out and replace specific sections of DNA.
Companies developing CRISPR
The CRISPR-Cas9 (CRISPR using the Cas9 enzyme) technique was first successfully adapted for genome editing in eukaryotic cells (cells which contain a clearly-defined nucleus, such as animal cells), in 2012 by a team at MIT led by Feng Zhang. In November of 2013, Zhang and five leading CRISPR researchers launched Editas Medicine with an initial €38.5 million in venture capital funding.
Zhang and MIT’s Broad Institute also beat out rival teams for a patent on the new technique. The rival teams, led by Jennifer Doudna of the University of California, Berkeley, and Emmanuelle Charpentier at the Helmholtz Centre for Infection Research in Germany, sued, and a four-year legal battle over the ownership of the CRISPR technology followed. The battle ended in September 2018, with a ruling by the U.S. Federal Circuit Court of Appeals that upheld the Broad Institute’s patent, paving the way for the widespread licensing of the technology and widespread investment.
Mitchell Ng, manager of the Thessalus biotech investment fund, pointed out in a 2018 Forbes article that CRISPR had the potential to completely alter the biotech landscape. “CRISPR is driving nearly all cutting-edge discoveries in biotech today, from cancer immunotherapy to gene editing,” she said.
In 2016, Time shortlisted the “CRISPR Pioneers” as their Person of the Year.
One major area for CRISPR research is in developing gene-based treatments for a variety of diseases. In October 2016, a lung cancer patient in China became the first human to receive cells modified using CRISPR. A gene that causes cancer cells to divide and multiply had been disabled in the cells. Other researchers have also used CRISPR to fight cancer by altering genes in patients’ immune systems.
In 2017, researchers at Temple University and the University of Pittsburgh used CRISPR to shut down the HIV virus’ ability to replicate. That same year, scientists at the Institute of Genetics and Developmental Biology at the Chinese Academy of Sciences used CRISPR to remove the genes that cause Huntington’s Disease from cells in mice. A team of researchers at the University of Texas Southwestern Medical Center has used a variation of CRISPR to correct the mutation that causes Duchenne muscular dystrophy, eliminating the mutation in living mice and in human cells growing in-vitro.
Editas is working on a CRISPR-based therapy for a common type of childhood blindness caused by mutations in genes responsible for vision. In 2017, a team of researchers at the University of Utah reported that they had used CRISPR to prevent the inflammation that causes chronic back pain.
Other researchers have focused on using CRISPR to alter organisms that carry disease. In 2016, a team at MIT proposed genetically modifying white-footed mice to make them immune to the bacteria that causes Lyme disease, and therefore unable to pass it along to ticks. Similarly, research teams at Imperial College London have suggested using CRISPR to reduce the fertility of the female mosquitoes, which carry malaria.
Progress has also been made in using CRISPR to alter crops. The Sainsbury Laboratory in Norwich, England, is using CRISPR to remove the genes that make potatoes and wheat vulnerable to disease, while geneticists at DuPont have used the technique to produce drought-resistant corn.
Perhaps most interesting for the future: In 2019, the University of Pennsylvania (UPenn) confirmed that they had treated two cancer patients using CRISPR gene editing to amplify another gene editing method, CAR-T.
As with most new genetic techniques, what scientists really need to know is whether it is safe for use in humans. In 2018, a paper was published in the journal Nature Biotechnology that described how some CRISPR gene editing led to unexpected insertions and deletions of the molecules that make up the genetic code, which could lead to genetic damage.
Bioethicists have also pointed out that CRISPR could be used to edit the human genome to produce customised babies. This fear was realised in 2018, when Chinese scientist He Jiankui announced he had used CRISPR to alter the genetic code of two human babies to supposedly give them resistance to HIV. His work was unsanctioned, and has led to calls for limits on the use of CRISPR to alter the human genome.
The future of CRISPR
Although CRISPR technology is only a few years old, new techniques are already being developed that are more efficient and possibly safer. In addition to CAR-T, techniques such as TALEN (transcription activator-like effector nuclease) and zinc finger nuclease, which involve engineering proteins to cut specific pieces of DNA, are being used to develop new therapies.
However, CRISPR-Cas9 is not only easier than these techniques, but also around 80 percent cheaper. For now, CRISPR remains the hottest genetic engineering technique in town.
14th August 2019