Illustration: Rebecca Zisser / Axios

The gene-editing tool CRISPR promises major scientific advances, but it has been held back by concerns about the precision of its editing and the ethics of making permanent changes to DNA. Now, two new scientific papers describe new tools that potentially get around these technical and ethical concerns.

Why it matters: CRISPR gene editing has the potential to cure many genetic illnesses. It's potential is only just being tapped, but so far it's been used to engineer better tomatoes, change the colors of butterfly wings, test for diseases and has even been used to edit human embryos. The main roadblocks have been the technical and ethical problems — which could be solved if the new techniques allow for more accurate and less risky gene editing.

Where it stands: Two papers published Wednesday, one in Science and another in Nature, describe the new tools. One demonstrated a way to edit a single letter, or base pair, of DNA. The other team used CRISPR to edit RNA, an ephemeral genetic material that isn't passed on to offspring.

Quick refresher: DNA consists of four letters, or nucleotides, abbreviated A, T, C and G. The A and T base pairs partner up, and the C and G pairs partner up. RNA is involved in the regulation, translation and expression of DNA, and consists of the base pairs G, C, A and U.

CRISPR in DNA: David Liu's research, published in Nature, builds on a gene editing technique he published last year. That method let scientists use Cas9, a CRISPR protein that targets DNA, to edit single base pairs instead of large chunks of DNA, greatly increasing gene editing precision. However, he could only change Cs to Ts and Gs to As, which is only half of the potential edits.

With Liu's new CRISPR, researchers can now edit in the opposite direction: T to C and A to G. In a press conference, Liu said these edits are analogous to using a pencil rather than cutting and pasting with scissors.

  • Single-letter mutations like these account for half of all genetic human diseases. Liu and his team used the new technique to correct mutations in bone cancer cells — with almost 50% effectiveness. That's a big step forward. ""It's a very worthwhile addition and it's here to stay," Erik Sontheimer of the University of Massachusetts Medical School in Worcester, told Jon Cohen at Science.

CRISPR in RNA: Feng Zhang, who was one of the first people to use CRISPR to edit DNA, has developed a similar technique that uses Cas13, another protein in the CRISPR family, to edit base-pairs in RNA. It allows scientists to convert A nucleotides into U nucleotides, which has the same effect as turning the A into a G.

  • Editing RNA alleviates some of the concerns involved with editing DNA. If DNA is thought of like a blueprint, any edits to it are permanent. But editing RNA allows scientists to edit the temporary notes from that blueprint without changing the original document, eliminating much of the risk. However, since RNA doesn't last forever, continuing treatment would be needed to combat any disease.

Some background: CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeat, is a precision gene-editing technique that hijacks systems used by bacteria to clip out the genetic material of viral invaders. Developed in 2013, it's vastly more effective than previous gene editors. In the years since, it's become almost ubiquitous in genetic engineering and is regularly considered a frontrunner for a Nobel Prize in science.

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