Targeted expression of a therapeutic agent is a major bottleneck in designing a drug delivery system. Protein aggregation and elevated oxidative stress are associated with the onset of many neurodegenerative disorders, including Huntington's disease (HD). An oxidative stress-inducible promoter, i.e. Thioredoxin 2, was employed to design a sensor for protein aggregation. RNA aptamers specific for mutant huntingtin were expressed only in cells where aggregation of mutant huntingtin occurred. A nine-fold increase in RNA expression was seen when aptamer sequences were cloned under the Trx2 promoter. Expression of aptamer resulted in reduced protein aggregation and decreased oxidative stress, which, in turn, reduced the expression of aptamers by two-fold. Reduction in aggregation led to increased cell survival. The aptamers were not expressed in cells expressing wild-type huntingtin in the soluble form. This rational and simple design will allow the use of this construct for the targeted expression of other therapeutic nucleic acid molecules as well.