The temperature sensitivity of vaccines and therapeutic proteins forces the distribution of life-saving treatments to rely heavily on the temperature-controlled (usually 2-8 degrees C) supply and distribution network known as the cold chain. Here, using avidin as a model, we demonstrate how surface engineering could significantly increase the thermal stability of therapeutic proteins. A combination of spectroscopic (Fourier transform infrared, circular dichroism, and ultraviolet-visible) and scattering techniques (dynamic light scattering, small-angle, and wide-angle X-ray scattering) were deployed to probe the activity, structure, and stability of the model protein. Temperature-dependent synchrotron radiation circular dichroism spectroscopy was used to demonstrate a significant increase in thermal stability, with a half denaturation temperature of 139.0 degrees C and reversible unfolding with modified avidin returning to a 90% folded state when heated to temperatures below 100 degrees C. Accelerated aging studies revealed that modified avidin retained its secondary structure after storage at 40 degrees C for 56 days, equivalent to 160 days at 25 degrees C. Furthermore, binding studies with multiple ligands revealed that the binding site remained functional after modification. As a result, this approach has potential as a storage technology for therapeutic proteins and the elimination of the cold chain, enabling the dissemination of life-saving vaccines worldwide.