Prolamins or gluten represents the major seed storage proteins in wheat grains, and are one of the most consumed dietary proteins in the world. Besides, gluten was also found responsible for a variety of diet-induced disorders in susceptible individuals. According to an estimate, about 1% of the world population is affected by gluten-induced disorders. The only effective therapy known so far is lifelong abstinent diet, which is difficult to practice if not impossible. In recent years, the public reliance on a wheat-based diet, especially in industrialized nations, has declined. The primary reason behind this trend is the increasing public awareness of the gluten-induced disorders and believe in the unsubstantiated reports documenting the health benefits of a gluten-free diet. As a result, the market for gluten-free commodities is continuously strengthening, which is projected to reach $7.59 billion by 2020. Based on our findings and the parallel research conducted elsewhere, we hypothesize that it is possible to develop a general therapy for gluten syndrome by eliminating or detoxifying the cause of these disorders. We tested our hypothesis by i) tissue-specific silencing of the wheat DEMETER and DRE2 genes, which respectively encode a DNA glycosylase and a Fe-S cluster biogenesis protein. These genes collectively control transcriptional activation of 100 different prolamins, except high molecular weight glutenins, and ii) ectopic expression of a glutamine specific endoprotease from barley and a post-proline cleaving endopeptidase from Flavobacterium in wheat grains. In the presentation, I will discuss the progress made on the above two objectives.