Introducing Cas9 Synergistic Activation Mediators (SAM)

CRISPR/Cas9 Synergistic Activation Mediator (SAM) is an engineered protein complex for the transcriptional activation of endogenous genes. It is based on the incorporation of MS2 RNA aptamers into the stemloop and loop two of the sgRNA that are exposed in the ternary Cas9 complex.

The SAM complex consists of three components:

  1. A nucleolytically inactive Cas9-VP64 fusion
  2. An sgRNA incorporating two MS2 RNA aptamers at the tetraloop and stem-loop
  3. The MS2-P65-HSF1 activation helper protein

The incorporation of three distinct activation domains - VP64, P65 and HSF1 – into the complex aids robust transcriptional activation through synergy.

SAM is capable of robust activation of coding as well as non-coding elements (lincRNA). For targeted activation of coding genes, please look at our activator sgRNA design tool.

SAM can further be combined with a human genome-wide library to activate all known coding isoforms form the RefSeq database (23,430 isoforms) for gain-of-function screening.

See: Konermann S*, Brigham MD*, Trevino AE, Joung J, Abudayyeh OO, Barcena C, Hsu PD, Habib N, Gootenberg JS, Nishimasu H, Nureki O & Zhang F. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature, doi:10.1038/nature14136.

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