A nucleic acid construct, comprising: (a) targeting arms for directing the nucleic acid construct to a target gene of a nucleic acid of a cell; (b) an actuating sequence that comprises a 3' splice acceptor followed by a reporter in sense orientation with respect to transcription of the target gene; (c) a drug selection cassette in sense or antisense orientation; (d) a nucleotide sequence of interest in antisense orientation; (e) a COIN (conditional by inversion element) in antisense orientation; and (f) recombinable units comprising: (i) a first pair of cognate recombinase recognition sites, R1/ R1', and a second pair of cognate recombinase recognition sites, R3/R3', recognized by a first recombinase; (ii) a third pair of cognate recombinase recognition sites, R4/R4', and a fourth pair of cognate recombinase recognition sites, R5/R5', recognized by a second recombinase; and (iii) a fifth pair of cognate recombinase recognition sites, R2/R2', recognized by a third recombinase, wherein the first, second, and third recombinases are not the same; wherein the actuating sequence and reporter is flanked upstream by R1, R2 is disposed between the reporter and the drug selection cassette, R3 is disposed between the drug selection cassette and the nucleotide sequence of interest, R4 is disposed between R3 and the nucleotide sequence of interest, R5 is disposed between the nucleotide sequence of interest and the COIN, R1' is disposed between R5 and the COIN, R3' is disposed between R1' and the COIN, R5' is disposed downstream of the COIN, R4' is disposed downstream of R5', and R2' is disposed downstream of R4'; wherein R1 and R1' are in opposite orientation, R2 and R2' are in the same orientation, R3 and R3' are in opposite orientation, R4 and R4' are in the same orientation, and R5 and R5' are in the same orientation (a) targeting arms for directing the nucleic acid construct to a target gene of a nucleic acid of a cell; (b) an actuating sequence that comprises a 3' splice acceptor followed by a reporter in sense orientation with respect to transcription of the target gene; (c) a drug selection cassette in sense or antisense orientation; (d) a nucleotide sequence of interest in antisense orientation; (e) a COIN (conditional by inversion element) in antisense orientation; and (f) recombinable units comprising: (i) a first pair of cognate recombinase recognition sites, R1/ R1', and a second pair of cognate recombinase recognition sites, R3/R3', recognized by a first recombinase; (ii) a third pair of cognate recombinase recognition sites, R4/R4', and a fourth pair of cognate recombinase recognition sites, R5/R5', recognized by a second recombinase; and (iii) a fifth pair of cognate recombinase recognition sites, R2/R2', recognized by a third recombinase, wherein the first, second, and third recombinases are not the same; (i) a first pair of cognate recombinase recognition sites, R1/ R1', and a second pair of cognate recombinase recognition sites, R3/R3', recognized by a first recombinase; (ii) a third pair of cognate recombinase recognition sites, R4/R4', and a fourth pair of cognate recombinase recognition sites, R5/R5', recognized by a second recombinase; and (iii) a fifth pair of cognate recombinase recognition sites, R2/R2', recognized by a third recombinase, wherein the first, second, and third recombinases are not the same;