When small tweaks aren’t enough and massive DNA interventions are needed, a new biotech tool inspired by a peculiar class of jumping sequences may come to the rescue. Barbara McClintock discovered mobile genes in the 1940s, and since then these transposable elements have never ceased to amaze.
PASTE is a three-part CRISPR tool invented at the MIT McGovern Institute for Brain Research. It’s composed of a modified CRISPR-Cas9 (it’s called nickase because it nicks a single DNA strand instead of cutting both) and two effectors: RT stands for reverse transcriptase (just like in prime editing) while LSR means large serine recombinase.
This brand-new molecular machine writes the genome in three steps. Step 1: the nickase finds the desired site. Step 2: the reverse transcriptase inserts a landing pad. Step 3: the recombinase lands there and delivers its large DNA cargo. The aim is to replace whole genes, when fixing mutations is not enough (one example is cystic fibrosis). Here are the links to learn more: