Move Over CRISPR/Cas9: Less-Known Tool Edits Gene Mutations

The CRISPR/Cas9 gene editing system, which uses a bacterial enzyme to slice DNA and insert new sequences, has exploded onto the scene in recent years, raising hopes of cures for devastating genetic disorders.

Now, though, a less well-known method of gene editing has cured an anemic disorder in mice. The method, which uses synthetic strands of DNA to trigger the cell’s own repair mechanisms, may be safer than CRISPR/Cas9 and easier to get into tissue.

The researchers from Yale Univ. and Carnegie Mellon Univ. use a synthetic peptide nucleic acid (PNA) that binds to a mutated section of DNA when inserted into a cell. PNA was developed in the early 1990s and sports the same nucleic acids — adenine, guanine, thymine, and cytosine — as DNA. But the backbone of PNA is a polyamide chain rather than the phosphodiester of DNA. More recently, researchers at the Univ. of Copenhagen developed PNAs with an additional decamer side chain.

“This jazzed-up PNA binds to DNA much stronger than DNA binds to DNA,” Glazer says. When introduced into the cell, the PNA wraps around the DNA double helix to create a triple helix. By altering the nucleic acids on the PNA, the researchers can program the molecule to bind to specific sections of a DNA strand.

The cell’s internal DNA repair molecules interpret a triple strand of DNA as a genetic error, which prompts them to snip the DNA at the point the researchers have flagged with the PNA strand. At the same time, researchers present the...