N2 - The use of Triticum timopheevii cytoplasmic male sterility (T-CMS) and Restorer-of-fertility (Rf) gene(s) in hybrid wheat breeding remains challenging. The main difficulty is the inconsistent fertility restoration by natural Rf genes. I hypothesised that poor binding of natural Rf proteins to their RNA target, orf279, may be a key factor. I tested this hypothesis by (1) verifying the predicted binding sites of natural Rf proteins using low- and high-throughput approaches; and (2) developing synthetic Rf proteins with enhanced binding affinity and specificity compared to natural Rf proteins. Consistent suppression of orf279 is essential for successful hybrid wheat breeding.