Patent ID: 8301387

Claim:
A method for combinatorially controlling the transcription of a target gene in a cell for producing a programmed response in the cell, the method comprising: identifying a plurality of logic functions, wherein each logic function combines two or more different inputs to generate an output comprising a unique gene expression in the cell; implementing at least one selected logic function that produces a desired genetic response when a combination of specified conditions are present, wherein the two or more different inputs comprise two or more regulatory proteins and the at least one selected logic function is implemented by producing interactions between the two or more regulatory proteins and interactive binding of the two or more regulatory proteins at DNA binding sites of the target gene to control a probability of promoter occupancy, wherein the target gene comprises one or more cis-regulatory regions having individual DNA binding sites, and wherein each DNA binding site has a binding strength and a binding location which are adjustable by varying composition of the one or more cis-regulatory regions to select one of a cooperative binding and competitive binding of the two or more regulatory proteins at the binding sites and one of a cooperative binding and competitive binding between the two or more regulatory proteins and polymerase; wherein the interactions comprise contact interactions and long-distance interactions that avoid interference between the DNA binding sites; wherein the desired genetic response in the cell comprises reporting or treatment of a disease or condition in which the two or more regulatory proteins are expressed; wherein each step of the method is executed on a transcription apparatus which corresponds to a computing machine; wherein the probability of promoter occupancy is determined according to the relationship P po =Z ON /(Z ON +Z OFF ), where Z ON and Z OFF are the total statistical weight of all states in which the promoter is occupied and unoccupied, respectively; wherein when the selected logic function is AND, Z ON =q o (1+ωq A +q B +2ω 2 q A q B ) and Z OFF =1+q A +q B +ωq A q B ; wherein when the selected logic function is OR, Z ON =q o (1+ωq A +ωq B +2ωq A q B ) and Z OFF =1+q A +q B +q A q B ; wherein when the selected logic function is XOR, Z ON =q o (1+ωq A +ωq B +2ωq A q B ) and Z OFF =(1+q A +q B +q A q B )×(1+q A +q B +ωq A q B ); and wherein when the selected logic function is NAND, Z ON =q o and Z OFF =1+q A +q B +ωq A q B ; where q o is the Boltzmann weight for promoter occupancy, q A and q B are ratios of the regulatory protein concentrations to the binding thresholds for input A and input B, respectively, and w is the mutual cooperativity factor.