We applied our Expanded Genetic Alphabet technology platform to the engineering of SYTX80-013-A: a site-directed, singly pegylated form of IL-2 completely lacking IL-2 receptor (IL-2R) alpha chain engagement yet retaining normal binding to the intermediate affinity beta-gamma IL-2R signaling complex present at the surface of natural killer (NK) and CD8+ tumor-killing cells. The gene discussed is IL2RA; the disease is neoplasm.