Ever since researchers first discovered that bacterial immune systems could be hijacked to selectively change DNA in living creatures, CRISPR gene-editing technology has been limited by the boundaries of the cell wall. CRISPR allows scientists to cut and paste little bits of DNA, swapping out even single letters of DNA to correct disease-causing genetic mutations. But – at least until now – all of that cutting and pasting has gone on inside cells.
A study published Thursday in the CRISPR Journal shows how scientists at Christiana Care Health System’s Gene Editing Institute in Delaware released CRISPR from behind the barricade of the cell wall. They were able to quickly make multiple changes to genetic code by extracting DNA from human cells and putting it into a test tube, where a protein called Cpf1 cut into the DNA and cleared the way for CRISPR to make edits.
But why would you want to do such a thing? Previous CRISPR tools limit gene-editing to short snippets of DNA within one single gene. Extracting the DNA from the cell could allow for more edits at one time.
In the more immediate term, the study authors said, this could have value in diagnosing cancer, replicating exact genetic mutations found in the tumours of individual cancer patients and identifying exactly what kind of cancer a patient has in order to develop a targeted treatment. The researchers are already working on commercialising such a diagnostic tool.
More significantly, though, the new technique could also pave the way for new gene-editing technologies that allow for removing and replacing entire faulty genes, not just little snippets of DNA. That could greatly expand the usefulness of CRISPR. At the moment, while the technology has shown great promise to cure diseases like sickle cell anemia, which is caused by a single-letter mutation, more complex diseases have seemed out of reach. This new technology could eventually change that.
But the breakthrough also speaks to the breadth of CRISPR technologies that have arrived in labs over the past year. The new tool relies on an enzyme known as Cpf1, rather than Cas9, the enzyme typically paired with the CRISPR system to cut up DNA. Discoveries of new CRISPR enzymes have helped to create a litany of new potential uses for the technology. For example, while Cas9 results in blunt ends when it slices through DNA, Cpf1 creates sticky ends that make it better suited for the removing larger chunks of genetic code.
The ability to edit outside of the cell, researchers said, could also reveal more about the mystery of how CRISPR actually works to modify the genome.
Recently, working with different enzymes has led to breakthroughs including editing the epigenome instead of making changes to DNA itself and using CRISPR to diagnose disease.
Such studies point to the power and potential of CRISPR — not just as a tool for altering the genome, but as a multifunctional powerhouse with uses we haven’t even yet imagined.