Northwestern Chemistry welcomes Alanna Schepartz from UC Berkeley, hosted by Xiaoyu Zhang.
Design rules for efficient endosomal escape
Although it has been known for more than 35 years that certain transcription factors can activate transcription when added to cells in culture, it has proven difficult to translate this finding into a robust strategy for therapeutic macromolecule delivery. Designing molecules that enter the endocytic pathway is not the problem - the problem is endosomal escape. This lecture will describe the discovery of a well-folded mini-protein that guides proteins and enzymes into the cytosol by promoting efficient endosomal escape, a single-molecule tool that quantifies this trafficking event in live cells with accuracy and precision, and cellular, structural, and biochemical experiments that together reveal what can be delivered and why many other delivery approaches have failed. This work provides new insights into how cells can purposefully respond to unnatural endocytic cargo and how this knowledge can be exploited to improve the cytosolic delivery of diverse proteins and enzymes.
Kelly Levander
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