Scientists from the Massachusetts Institute of Technology (MIT) have designed a gene editing tool that has the potential to detach faulty genes and replace them with new ones safely and efficiently. The tool, known as PASTE, holds the potential for treating diseases caused by defective genes.
The science and other stuff to know
Detailed in the journal Nature Biotechnology, PASTE, also called Programmable Addition via Site-specific Targeting Elements, combines the precise targeting of CRISPR-Cas9 with enzymes known as integrases to cut and replace faulty genes.
For this study, MIT scientists focused on serine integrases. These enzymes can insert huge chunks of DNA, as large as 50,000 base pairs. They also target specific genome sequences known as attachment sites. When they find the site in the host genome, they bind to it, integrating their DNA payload.
“Just like CRISPR, these integrases come from the ongoing battle between bacteria and the viruses that infect them,” Jonathan Gootenberg, one of the study authors, said in a statement.
In a series of tests, the research team used PASTE to work on human liver cells, T cells, and lymphoblasts, inserting 13 different genes into nine locations in the genome. In the tests, the success rate was up to 60 percent. What’s more, the new technique generated very few errors at the site of gene integration. The team also demonstrated gene insertion into about 2.5 percent of “humanized” liver cells in mice.
Not only is PASTE more gentle and potentially safer, but the research team says it can insert huge amounts of DNA at once. In this study, researchers inserted up to 36,000 base pairs, but they believe even longer sequences could also be inserted.
Thus, PASTE could be particularly useful in treating diseases caused by faulty genes such as cystic fibrosis, hemophilia, G6PD deficiency, or Huntington’s disease.
“It’s a new genetic way of potentially targeting these really hard-to-treat diseases,” Omar Abudayyeh, a McGovern Fellow at MIT’s McGovern Institute for Brain Research, said in a statement. “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.”
More research is still needed before PASTE is approved for treating diseases and disorders caused by faulty genes. Meanwhile, MIT scientists have made their genetic constructs available for other researchers to use.