Earlier this year, Chinese scientists made headlines when they used a gene-editing technique to modify the genomes of human embryos for the first time.
But the new technique, which has been called the “biggest biotech discovery of the century,” comes with side effects, including dangerous mutations, or genetic tweaks, that could result in disease or even death.
Now, scientists think they have found a way to prevent some of these unintended consequences, according to a new study published yesterday in the journal Human Gene Therapy.
To understand these consequences, first you have to understand the technique itself.
Known as CRISPR-Cas9, the technique is basically a way to “cut and paste” bits of DNA into a gene. It was discovered accidentally by Jennifer Doudna, a biochemist at the University of California, Berkeley, and her collaborator, Emmanuelle Charpentier of the Helmholtz Centre for Infection Research in Germany.
How gene editing works
Bacteria have been using this technique for millions of years to protect themselves from viruses. When they detect some of a virus’s DNA, they cut and paste it into their own genomes, so they can recognise the invaders next time they encounter them.
A few years ago, Doudna and her colleagues realised that this naturally occuring cut-and-paste process could be used to change the DNA sequence of any cell. This is a game changer: It means you could potentially cut out a faulty gene and replace it with a healthy version.
Unfortunately, the process can result in some genetic mutations, or tweaks in the order of the pairs that make up a strand of DNA. And even the tiniest of mutations can have deadly consequences: a mutation in a single gene can cause cystic fibrosis, a life-threatening disorder of the lungs and digestive system. Alternatively, the mutations could be beneficial. In these cases, scientists who want to cause a specific mutation could swap in the desired DNA sequence for the DNA that was cut out.
So far, the technique has been used in cows, pigs, monkeys, and, at least in one controversial recent study, humans.
Many researchers have expressed strong concerns about the ethics and safety of tinkering with human embryos, even though these particular embryos were chosen because they were unable to survive. For one thing, when the Chinese researchers used the technique, it produced far too many errors to be considered safe for medical use in humans.
A step toward making it safer?
Researchers at Harvard Medical School said this week that they have found a way to reduce the number of these unwanted mutations by 40%.
The study involved two kinds of human cells: cancer cells (which are important for their ability to grow and reproduce quickly and are often used for genetics studies) and embryonic stem cells (which are important for their ability to develop into any type of tissue and are useful for studying human development).
The process involves two key differences:
- First , the researchers used a special version of the Cas9 enzyme that binds to the DNA but can’t cut it. Because of this characteristic, the enzyme is said to be “dead.” To cut the DNA, t hey used another enzyme, called Fok1 nuclease, which consists of two pieces that bind together . This change makes it a much more accurate method for targeting a specific DNA sequence, the researchers write in their paper.
- Next, the researchers used shortened versions of the guide RNAs (the genetic strands that target a desired part of the genome) to find the DNA they wanted to modify. In their study, using these shorter RNAs still produced the desired changes in the DNA, but with fewer unwanted mutations.
To measure how accurate their method was, the team used a genetic sequencing technique they developed themselves which looks for unintended breaks in both strands of the DNA.
Even though the modified technique reduced a significant amount of unwanted mutations, there were still stray mutations in two parts of the DNA, the researchers noted.
Here’s a video that describes the basic gene-editing technique:
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