Computer-assisted engineering of stable human leukemia inhibitory factor

Abstract

Due to their capacity for long-term expansion and differentiation potential, embryonic stem cells (ESC) can be selected as seed cells for generating cultured meat. Leukemia inhibitory factor (LIF) is a pleiotropic cytokine with a wide range of activities, including maintaining ESC in a totipotent state in vitro, which is an essential additive component of the ESC proliferation medium. However, owing to the low thermal stability of wide-type human LIF (hLIF-WT), the cost was increased by repeatedly added and storage loss. Here, we tackle this problem using a computer-assisted protein engineering strategy to create a unique modified hLIF with three mutations displaying unprecedented stability and enhanced biological function. The molecule holds considerable promise for stem cell research and the cultured meat field.