New paper on engineering allosteric control of Cas9 in Nature Biotechnology

A big congrats to Ben et al. on their paper dropping today in Nature Biotechnology! This work uses randomized domain insertion to explore the 'malleability' of Cas9 for protein fusions. Surprisingly, Cas9 is a robust structure that can accept insertions throughout the protein and remain functional, even as surprising positions such as the middle of alpha helices, etc. Taking this one step further, Ben use this trick to isolate a novel Cas9-estrogen receptor ligand binding domain fusion that is allosterically regulated by small molecule. This system therefore represents a simplified tool for controlling Cas9 activity with a well-characterized ligand. If you're interested in finding out more check out:

Oakes BL, Nadler DC, Flamholz A, Fellmann C, Staahl BT, Doudna JA, Savage DF. 2016. Profiling of engineering hotspots identifies an allosteric CRISPR-Cas9 switch. Nat Biotechnol.

Figure 1 from Oakes et al. showing the malleability of Cas9 to domain insertion.

Figure 1 from Oakes et al. showing the malleability of Cas9 to domain insertion.