Design of Enhanced Endosomal Escape Domains for Delivery of Macromolecules into Cells

Background

Macromolecular peptide, protein and oligonucleotide therapeutics have great potential to treat human disease; however, due to their size, they have no ability to enter cells. Peptide/Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), promote uptake of macromolecules via endosomal macropinocytosis. However, overcoming the rate-limiting step of endosomal escape remains the major challenge.

Technology Description

UC San Diego researchers have designed an Endosomal Escape Domain (EED) that resulted in a significant enhancement of cytoplasmic delivery in the absence of cytotoxicity. In addition they developed an assay to measure transduction into the cytoplasm to compare and contrast PTDs/CPPs.