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The global output of cottonseed contains ∼10.8 trillion grams of protein that can meet the basic protein requirements of ∼590 million people at a rate of 50 g/day. However, gossypol, a toxic terpenoid present in seed glands, renders cottonseed unfit as food for human consumption or as feed for nonruminants. RNAi, under the control of a seed-specific promoter, was used to selectively silence δ-cadinene synthase gene to reduce gossypol levels in the seed by 97% without affecting the levels of gossypol and related terpenoids in rest of the plant where they are needed for defense against insects and diseases. The resulting Ultra-low Gossypol Cottonseed (ULGCS) is considered safe as food or as feed for more efficient (both, in terms of feed conversion ratio and protein conversion ratio) monogastric animals. Field trials conducted over multiple years in multiple states confirm the stability and heritability of the trait with no diminution of fiber/seed yield, quality or agronomic performance. A ULGCS event, TAM66274, was deregulated by USDA-APHIS in October 2018 and FDA concluded its food safety consultation in September 2019 and concurred with our determination of its safety. Global adoption of TAM66274, with more efficient and expanded usage of its protein, has the potential to significantly improve nutrition security and boost farmers' income without requiring additional inputs or acreage under cultivation, thus making cotton farming more sustainable. [ABSTRACT FROM AUTHOR]