Over just a few short years the CRISPR gene-editing technique has revolutionized science, affecting everything from medicine to agriculture. Two new breakthrough studies have just been published describing dual methods that make the process more precise and efficient paving the way for scientists to safely alter DNA mutations that cause thousands of different human diseases.
CRISPR is conventionally a cut-and-paste tool allowing scientists to chop out unwanted strands of DNA and insert new genes, but a large volume of human diseases are caused by a single point mutation somewhere in a person's DNA. Up until now scientists have not been able to simply and directly erase or rewrite these single mutations in living human cells.
Our human genome consists of 3 billion base pairs made up of chemical units referred to by the letters A, C, G and T. There are 50,000 known genetic mutations that are linked to disease in humans and 32,000 of these are single point mutations. Half of those single point mutations have been identified as a G-C pair that has mutated into an A-T pair.
One of the exciting innovations recently revealed comes from a team at the Howard Hughes Medical Institute. The scientists built a new enzyme referred to as a "base editor." This base editor can essentially reverse or rewrite specific base pair mutations.
"CRISPR is like scissors, and base editors are like pencils," says David Liu of this new innovation.
In the team's early experiments with base editing a specific mutation associated with the disease hemochromatosis was successfully fixed. No unwanted off-target effects were identified and the base editor enzyme operated with greater than 50 percent efficiency.
"We are hard at work trying to translate base editing technology into human therapeutics," Liu says.
The second new CRISPR innovation revealed recently comes from a collaborative team of Broad Institute and MIT scientists. For the first time the team discovered a way to accurately edit RNA base pairs in human cells.
Dubbed "REPAIR" this system also focuses on base editing but this time is targeted at RNA. Unlike permanent changes to DNA, RNA is much more ephemeral and even reversible. The ability to edit RNA in human cells opens up an entirely new world of disease treatments targeting conditions including diabetes and IBD.
"REPAIR can fix mutations without tampering with the genome, and because RNA naturally degrades, it's a potentially reversible fix," explains co-first author David Cox.
Both of these gene-editing breakthroughs offer incredible new precision in developing targeted treatments for a vast array of human diseases that are founded on single genetic mutations. Despite both studies only experimenting on cells in vitro these are fundamental innovations that will potentially reframe the next century of human medicine.
The Howard Hughes Medical Institute study was published in the journal Nature.
The RNA editing study was published in the journal Science.