Professor Christopher A. Alabi

Professor Christopher A. Alabi
Robert Frederick Smith School of Chemical and Biomolecular Engineering
Cornell University

Intracellular Delivery of Proteome-Modulating Peptides and Proteins

Peptide- and protein-based therapeutics represent a rapidly expanding class of pharmaceuticals, yet their clinical impact remains largely limited to extracellular targets. Unlocking their full potential for intracellular applications requires effective delivery strategies. Molecular degraders, particularly peptide-based degraders (PepTACs), offer a promising approach for targeted protein degradation, leveraging expanded interaction surfaces and structure-guided design. However, their translation is hindered by poor stability and limited cellular permeability. 

In this talk, I will present recent advances in intracellular delivery of proteins and PepTACs using anionic cloaking and amphiphilic loading strategies with lipid-based carriers. By harnessing anionic tags or hydrophobic interactions to drive lipid nanoparticle (LNP) encapsulation, we achieve efficient cytosolic transport of functional degraders and therapeutic proteins, including antibodies and peptides targeting β-catenin in Wnt-driven cancers. This platform enhances intracellular delivery while enabling the repurposing of biologics for new therapeutic applications. Collectively, these strategies establish a generalizable framework for improving intracellular access to peptide- and protein-based therapeutics, expanding their potential for targeted proteome modulation.

Lean more about the Chemical Biology Colloquium and see the full schedule