Choosing the right tool for precise genome editing – published in Nature Reviews Molecular Cell Biology

The genome-editing toolbox is rapidly expanding, offering increasingly diverse ways to make precise changes to DNA. But with so many emerging technologies, how do we choose the right tool for a particular application—and where does homology-directed repair (HDR) fit within this changing landscape?

In a new Comment published in Nature Reviews Molecular Cell Biology, Postdoc Eric Aird and Jacob discuss the current and future role of Cas-induced HDR alongside emerging genome-editing technologies.

New technologies are increasingly specialized for different types and sizes of genetic modification. Base, prime and DNA polymerase editors are particularly well suited to small sequence changes, while emerging approaches such as prime assembly, CASTs, large serine recombinases and bridge recombinases are opening possibilities for much larger modifications. HDR, however, occupies a particularly broad space in this toolbox, enabling precise modifications ranging from individual base pairs to kilobase-scale sequences.

No single editing technology is likely to be optimal for every application. Choosing an approach requires balancing not only the desired modification and its size, but also precision and outcome purity, cell type, design complexity, delivery, time, cost and ease of use. As newer technologies continue to mature, HDR therefore remains an important and versatile option rather than simply being replaced by the latest generation of editors.

The Comment provides a perspective on how these complementary technologies may shape the future of precise genome editing and emphasizes an increasingly important question for the field: not simply whether we can make a particular edit, but which tool is best suited to make it.

Check out the Comment in Nature Reviews Molecular Cell Biology!