Joint ChemBio and Synthesis RIG Seminar - Chemical Biology Tools for Measuring Drug Delivery

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• Joshua Kritzer (Tufts University)
• Friday 23 May 2025, 14:00-15:00
• Dept. of Chemistry, Wolfson Lecture Theatre.

If you have a question about this talk, please contact Jasmine Mitchell.

Large-molecule therapeutics including peptides, oligonucleotides, and proteins make up a large and growing portion of the drug development pipeline. One of the greatest barriers to developing these drugs is cell penetration. Most enter the cell through a complex pathway involving endocytosis followed by endosomal escape. This process is so poorly understood and difficult to study that it is challenging simply to measure how much compound has actually accessed the cytosol at any given point. The Kritzer Lab has developed new tools for making these and related measurements. The Chloroalkane Penetration Assay (CAPA) is a versatile assay that measures cell penetration using cellularly expressed HaloTag protein and a small chloroalkane tag on the molecule-of-interest. CAPA has been used by the Kritzer group to measure cell penetration for many classes of peptide and oligonucleotide therapeutics, to measure penetration to different subcellular compartments, and to measure relative penetration in different cell types. CAPA has also been adopted by academic and industrial groups all over the world to investigate cell penetration. The Kritzer group has also used molecular evolution to produce new HaloTag variants which work optimally with a fluorogenic benzothiadiazole dye. The resulting “BenzoTag” system allows for turn-on, no-wash cell labeling in seconds. BenzoTag is currently being applied to produce a “turn-on” version of CAPA for continued investigation of drug delivery and mechanisms of endosomal escape

This talk is part of the Synthetic Chemistry Research Interest Group series.

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