We've been using CRISPR for years – now we know how it really works
A storm of criticism met the claimed creation of the first genome-edited children in China last month. One reason is that the twin girls have unpredicted new mutations whose effects are unknown. But it now appears there's a really easy way to ensure the CRISPR genome editing technique makes far more precise, predictable mutations.
The term "CRISPR genome editing" is really a bit of a misnomer. The method is most commonly used to disable genes by cutting the DNA in a specific site. When the cell repairs the cut, it typically adds or removes one or more DNA letters. But Paola Scaffidi of the Francis Crick Institute in London suspected that these mutations might not be as random as they appear. To find out, her team induced mutations in 1500 target sites in human cells growing in a dish.
They found a stunningly simple pattern. "We started with machine learning but we did not need it," Scaffidi says. It appears the sequence of the RNA that guides the CRISPR Cas9 protein to its target is crucial. If the fourth DNA letter from the end is a G, the resulting mutation is indeed relatively random. But if it's an A, T or C the outcome is more predictable. If it's a T, for instance, in 9 out of 10 cells a single extra T will be inserted at the target site.
If the findings are confirmed, it means the thousands of biologists around the world using CRISPR for research can make it far more precise and powerful simply by altering the guide RNAs they use. It also greatly boosts the prospects for using CRISPR to treat all kinds of disorders by correcting disease-causing mutations inside the body.
Also at The Francis Crick Institute.
Target-Specific Precision of CRISPR-Mediated Genome Editing (open, DOI: 10.1016/j.molcel.2018.11.031) (DX)
(Score: 2) by takyon on Thursday December 13 2018, @11:14PM
Maybe right now if you have the keyword codebook.
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