Abstract: Provided are methods for determining that a candidate polypeptide in a library of polypeptides has editing activity comprising expressing in a plurality of cells: a library of first expression cassettes each comprising a nucleic acid encoding a polypeptide wherein each polypeptide in the library comprises, a first editing domain, a first linker, a nuclease-deficient RNA guided endonuclease domain, a second linker, and a second editing domain; and a second expression cassette comprising a nucleic acid encoding a guide RNA directed to a target of interest, wherein said first and second expression cassettes are expressed in the plurality of cells; separating the plurality of cells based on the expression level of the target of interest; extracting genomic DNA (gDNA) from the plurality of cells; and sequencing the gDNA of cells that have a high level expression or a low level of expression of the target of interest.

Abstract: Provided herein are, inter alia, compositions and methods for modulating gene expression.