Engineering cytosolic transport for improved therapeutic delivery

Biopharmaceuticals have transformed modern medicine by enabling unprecedented biological control over disease beyond the capabilities of small molecule drugs. Biological drug applications are highly diverse and represent most of the top-selling drugs worldwide. However, inefficient drug delivery to the interior of cells has limited development for intracellular applications. This poses a substantial area to expand the possibilities of biopharmaceuticals. This thesis develops sensors to quantify intracellular pH and cytosolic delivery efficiency as well as a directed evolution methodology to discover more efficient endosomal escape peptides. Together, these tools may enable more effective intracellular biopharmaceutical delivery to improve human health.