Sorghum (Sorghum bicolor) is the fifth most important cereal crop in the world after wheat, rice, maize and barley. Unfortunately, sorghum has a much poorer nutritional profile than maize; for example, a lower content of the essential amino acids lysine, threonine, tryptophan and of sulphur, and a much lower bioavailability of protein, starch, iron and zinc. Classical breeding of sorghum for nutrition has limited applicability owing to the absence of easily transferable traits within the sorghum gene pool. We have therefore adopted a transgenic approach to produce improved sorghum germplasm, which we hope will entail a positive factor in the economics, nutrition and diets of African populations residing in the harsh tropics and subtropics, where, agronomically, other crops do not perform as well as sorghum. Lysine biofortification was targeted for the sole reason that it has a pharmacological use much more specific than that of most other amino acids and that human beings cannot synthesize it. The project will develop, test and use iRNA and tRNAlys codon substitution strategies to increase the concentration of lysine-containing proteins in sorghum grain. To mitigate unintended negative pleiotropic responses, we will pay close attention to other kafirins loci, which are involved in the modifier effect and in maintaining the vitreous nature of the grain through their involvement in central structural roles. This project therefore presents an insight into the molecular aspects of sorghum kafirins and metabolic pathway engineering, and at the same time emphasizes precision in genetic manipulation to ensure high yields and quality, and product safety for the environment, and for animal and human health.