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A new tool for editing DNA, one base at a time

Deborah Netburn, Los Angeles Times on

Published in Science & Technology News

There are 3 billion base pairs in the human genome, and a mistake or mutation in just one single letter can have a significant impact on a person's health.

Of more than 50,000 genetic changes currently known to be associated with disease in humans, 32,000 of those are caused by the simple swap of one base pair for another, Liu said.

The group's first base editing tool, which had the effect of converting a C to a T, has the potential to correct 14 percent of human diseases associated with a single-letter mutation. The new tool will allow researchers to address an additional 48 percent of these types of diseases.

The type of mistake that can be targeted by the new base editor is "by far, the most common kind" in people "and probably all living systems," Liu said.

The team's new base editor can fix these genetic errors by rearranging the atoms in a single faulty A and turning it into an I. The editor can also alter the T that was paired with the original A in the double-stranded helix of DNA and turn it into a C, Liu said.

Like the previously described base editing system, the new editor relies on the CRISPR-Cas9 complex to locate a specific sequence of bases within a genome and bond to it. Normally, CRISPR-Cas9 would then make a double cut in the DNA and either insert or delete genetic information, but Liu's group uses a crippled form of CRISPR that can't make a cut.

Instead, it pulls the DNA strand away from its partner, allowing an enzyme attached to the CRISPR system to change the base at the target site.

Although Liu and his lab partners had successfully engineered one base editor before publishing their most recent work, they faced fresh challenges when they set about creating an editor that could alter an adenine.

In previous work, the team took gene-editing tools found in nature and then synthesized them to create a targeted single base editor.

Unfortunately, nature doesn't make an enzyme that can convert an A to an I in DNA. That meant they had to evolve one in the lab.

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