When a chef develops a new recipe, they methodically add and remove individual ingredients to see how each of them alters the final dish. When scientists try to understand the role of genes in the body, they employ a similar tactic using genome editing. Currently, the most popular tool in their toolbox is CRISPR, with applications ranging from cancer therapeutics to treatments for genetic diseases like sickle cell anemia and β-thalassemia. However, this genome editing staple still has its limitations.
“It’s really hard to pack the genes encoding these proteins into the viruses that are used for their delivery into the cells,” said Tautvydas Karvelis, a genome biologist at Vilnius University. Even when CRISPR nucleases are directly delivered into cells, their large protein sizes present limitations. For example, the commonly used Cas9 is about 1,400 amino acid residues long.
In a recent study published in Nature Methods, Gerald Schwank, a genome biologist at the University of Zurich, and his team described a tiny, but efficient, nuclease that works as well as some of the current Cas proteins but is less than half their size.
“It’s like a new class of tools that can be used for genome editing, not just as a principle,” said Karvelis, who was not involved in the study.
In 2021, Karvelis discovered a compact RNA-guided protein capable of cutting DNA: TnpB. Compared to other CRISPR nucleases, TnpB is much smaller with approximately 400 amino acid residues. However, TnpB has a lower editing efficiency and limited target range.
By Sahana Sitaraman, PhD
Article can be accessed on: The Scientist