New gene-editing technology successfully cures a genetic blood disorder in mice

A next-generation gene-editing system developed by Carnegie Mellon University and Yale University scientists has successfully cured a genetic blood disorder in living mice. 

Unlike the popular CRISPR gene-editing technique, the new technology can be administered to living animals and it significantly decreases unwanted, off-target gene mutations. The findings, reported in Nature Communications, offer a new therapeutic approach to treat genetic diseases of the blood like beta thalassemia and sickle cell disease by targeting faulty genes in hematopoietic stem cells.

The novel system relies on state-of-the-art peptide nucleic acid (PNA) molecules, a synthetic nucleotide technology that has been pioneered at Carnegie Mellon's Center for Nucleic Acids Science and Technology (CNAST).

"We have developed a system that uses FDA-approved nanoparticles to deliver our PNA molecule along with a donor DNA to repair a malfunctioning gene in living mice. This has not been achieved with CRISPR," said Danith Ly, professor of chemistry in Carnegie Mellon's Mellon College of Science and an expert in PNA chemistry.

Gene-editing technologies like CRISPR rely on DNA-cutting enzymes to slice open DNA at a target site to edit a specific gene. The problem with this is twofold. First, the enzymes are large and therefore difficult to administer directly to living animals, so scientists typically remove the cells, treat them in the lab and then put them back into the body. Second, once inside a cell, the enzymes could indiscriminately cut DNA at sites other than the original gene target.

The new Carnegie Mellon/Yale system avoids both of these issues. The new system consists of biocompatible nanoparticles containing PNAs, small nano-sized synthetic molecules in which a protein-like backbone is combined with the nucleobases found in DNA and RNA. PNA is designed to open up double-stranded DNA and bind near the target site in a highly specific manner without cutting anything. And the PNAs easily fit inside the nanoparticle delivery system, which is FDA-approved and has already been used to treat neurodegenerative diseases in humans.