Drug-tunable multidimensional synthetic gene control using inducible degron-tagged dCas9 effectors

作者：Kleinjan Dirk A; Wardrope Caroline; Sou Si Nga; Rosser Susan J^*

来源：Nature Communications, 2017, 8(1): 1191.

DOI：10.1038/s41467-017-01222-y

The nuclease-deactivated variant of CRISPR-Cas9 proteins (dCas9) fused to heterologous transactivation domains can act as a potent guide RNA sequence-directed inducer or repressor of gene expression in mammalian cells. In such a system the long-term presence of a stable dCas9 effector can be a draw-back precluding the ability to switch rapidly between repressed and activated target gene expression states, imposing a static environment on the synthetic regulatory circuits in the cell. To address this issue we have generated a toolkit of conditionally degradable or stabilisable orthologous dCas9 or Cpf1 effector proteins, thus opening options for multidimensional control of functional activities through combinations of orthogonal, drug-tunable artificial transcription factors.

• 出版日期2017-10-30