In vivo gene sensors

摘要

Described are methods and compositions for the detection of target genes. The inventors have developed a synthetic nucleic acid sensor-effector gene circuit. In cells without a target gene, the circuit suppresses e.g., effector production, but in the presence of the target gene the suppression is subject to competition, such that the synthetic sensor is de-repressed and permits expression of the effector gene. The methods and compositions described further permit the selective expression of an effector gene in those cells expressing the target gene. In this manner, cells expressing a target gene can be selectively targeted for treatment or elimination. In certain aspects, the methods and compositions described permit the selective expression of an agent such as a therapeutic gene product, in a specifically targeted population of cells in an organism.

主权项

1. A method of detecting a bacterial cell expressing a target gene comprising the steps of:
a. introducing to said bacterial cell a nucleic acid construct encoding a portion of said target gene sequence, fused to an effector gene sequence, and a construct encoding an inhibitory nucleic acid sequence directed against at least said portion of said target gene sequence, wherein in the absence of said target gene, said inhibitory nucleic acid sequence supresses effector gene expression; and b. monitoring expression of said effector gene sequence in said cell and comparing the level of effector gene expression to a reference level, wherein if expression of said effector gene is increased relative to said reference level, said target gene is detected, thereby detecting the bacterial cell.