Genetics is having a moment in the sun. Last year, biologists at the University of Bath in England created mice with neon feet. Scientists edited human embryos for the first time in the United States in August, cutting out a mutation for a heritable heart disease. Earlier this month, research spearheaded by the Chinese Academy of Sciences produced leaner pigs — a harbinger, one imagines, of low-fat bacon.

Each of these feats required a laboratory tool called CRISPR-Cas9, often shortened to CRISPR. The gene-editing system hunts for a specific section of DNA and snips it out. CRISPR surged through molecular biology labs on a wave that began five years ago, when about 150 published scientific papers had CRISPR in their titles. By 2016, that figure was in the thousands.

And the geneticist's toolbox has gained two shelves, researchers at the Broad Institute in Cambridge, Mass., announced Wednesday. One new method, reported in the journal Science, manipulates a different sort of genetic information: RNA, not DNA. The other method, reported in Nature, is capable of subtle DNA changes — a tweak of a single point rather than a chop through DNA's double helix.

Although the two studies were unrelated, both tools involved share similarities with CRISPR. They are easy to use, the authors say. And they lock onto their genetic targets like microscopic homing missiles.

Eugene Koonin called the RNA tool “an excellent advance.” Koonin, a genomics researcher at the National Institutes of Health who was not involved with this research, said the RNA editor could be used to treat conditions “that are short term in nature, such as local inflammation and the like.”

RNA carries genetic information from DNA throughout a cell, allowing the cell to make new proteins. It's a bit like a person who ducks into a library, records instructions from a book and runs back out to share notes. CRISPR permanently alters an embryo's genome. But any changes via RNA manipulation are temporary. Even if you erase part of the notebook, the original text in the library stays intact.

British scientists are testing cutting edge gene editing techniques in mice by inserting a jelly fish gene that makes their skin green. (Reuters)

“Each of us carries two sets of 3 billion base pairs of DNA, one set from Mom and one set from Dad, in almost all of our cells. This human genome is predominantly made of just four letters: A, C, G and T,” David Liu, a chemistry professor at Harvard University and author of the Nature report, told reporters Tuesday. Those letters always pair up, A with T and G with C.

Errors in the genetic code in which one pair swaps for another, a change called a point mutation, can be disastrous. “By far the most common kind of disease-associated point mutation in humans, and probably in all living systems, is the mutation of a G-C base pair into an A-T base pair,” Liu said. “This class of mutation, changing G-C to A-T, accounts for about half of the 32,000 known pathogenic point mutations in humans.” Both of the new tools are single-base editors, aimed at reversing these point mutations.

The RNA tool focuses on a single type of mutation in the alphabet of the genetic code. “If you look at genetic diseases that are caused by single-letter mutations in the DNA, G to A mutations account for more than 40 percent, almost half, of all the mutations,” said Feng Zhang, an author of the Science study and a molecular biologist at the Broad Institute, a biomedical research facility that is a partnership between the Massachusetts Institute of Technology and Harvard.

A few years ago, Zhang and his colleagues began working with a bacterial protein called Cas13. Like Cas9, this enzyme cuts through genetic information, although it slices RNA instead of DNA. In the new study, the authors mutated the Cas13 enyzme. Bacteria used the Cas13 protein as a molecular butcher knife to trim invading viral RNA from the meat of the genome.

The scientists mutated the protein to bind to mammalian RNA without destroying it. Once bound, the new method made a single modification, changing the letter A to I (which a cell interprets as G). In other words, if DNA mutates from G to A, this tool effectively halts the mutation at the RNA level. The authors of the Science report named the new system REPAIR: RNA Editing for Programmable A to I Replacement. REPAIR successfully converted A to I at target sites at an average rate of 20 percent to 40 percent.

“The RNA base-editing work from Feng Zhang's laboratory is an impressive and exciting development from an outstanding and highly productive research group,” said Liu, also a Broad Institute and Howard Hughes Medical Institute researcher.

Although it is far from ready as a therapy, Zhang said that he envisions such a tool being utilized in doses. It could be useful for cells that no longer replicate, like those in the brain.

“One of the major concerns about DNA editing is that once you make a permanent change it's hard to undo it,” he said. “Whereas with RNA, once you stop giving the RNA editing REPAIR system then those changes will be reverted back.” (It's the difference between constructing a car with a more powerful engine, vs. deflating tires when you want to drive over sand and reinflating them when you hit pavement.)

Likewise, Liu and his colleagues created a new way to change a single DNA base. For two years, Nicole Gaudelli, a Harvard University postdoctoral researcher, attempted to create a protein that did not exist in nature. She forced E. coli bacteria, over seven generations, to evolve a protein that swaps the A-T base pair to a G-C pair.

If scientists wield CRISPR like scissors to cut DNA, Liu said, this base editor is the genetic equivalent of a pencil writing in the correct letter where there was previously a mutation. “It's important to point out that for some applications, scissors are the best tool for the job,” he said, “while for other applications such as fixing a single letter in DNA, a pencil is best.”

These discoveries come on the heels of a bruising patent fight over ownership of CRISPR, which has pitted the Broad Institute against the University of California at Berkeley. Liu, Gaudelli and a third author, Alexis Komor, filed patent applications related to the single-base DNA editor. Zhang and three of his co-authors filed patent applications related to the REPAIR system.

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