Assessment of combinatorial configurations for gene silencing. (a) Scheme depicting the insertion of combinations of effector domains. (A) Combinatorial dual-effector constructs. (b) Summary of silencing capabilities of dual-effector constructs alone (A, blue) and in combination with cognate third effector (B, yellow). (A) Dotted lines show experimental silencing values of the relevant two domains on separate dCas9s. Dashed red line indicates silencing value of using all three domains on separate dCas9s. (c) (A) Depiction of strategy to introduce KRAB at N-terminus of dCas9 to create all-in-one constructs. (B) Silencing activity of all-in-one constructs.