New CRISPR-based tool inserts large DNA sequences at desired sites in cells

Building on the CRISPR gene-editing system, MIT researchers have designed a new tool that can snip out faulty genes and replace them with new ones, in a safer and more efficient way.

Using this system, the researchers showed that they could deliver genes as long as 36,000 DNA base pairs to several types of human cells, as well as to liver cells in mice. The new technique, known as PASTE (Programmable Addition via Site-specific Targeting Elements), could hold promise for treating diseases that are caused by defective genes with a large number of mutations, such as cystic fibrosis.

"It's a new genetic way of potentially targeting these really hard to treat diseases," says Omar Abudayyeh, a McGovern Fellow at MIT's McGovern Institute for Brain Research. "We wanted to work toward what gene therapy was supposed to do at its original inception, which is to replace genes, not just correct individual mutations."

The new tool combines the precise targeting of CRISPR-Cas9, a set of molecules originally derived from bacterial defense systems, with enzymes called integrases, which viruses use to insert their own genetic material into a bacterial genome.

"Just like CRISPR, these integrases come from the ongoing battle between bacteria and the viruses that infect them," says Jonathan Gootenberg, also a McGovern Fellow. "It speaks to how we can keep finding an abundance of interesting and useful new tools from these natural systems."

Image source: Unsplash/CC0 Public Domain.