The Science Behind Entrada

Endosomal Escape Vehicle (EEV™) technology

Entrada’s EEV technology improves bioavailability, biodistribution, intracellular delivery and endosomal escape

Biologics generally cannot enter the cell

Many proteins, peptides and oligonucleotides have highly potent and specific biological activities

These molecules are usually hydrophilic and large in size, are unable to penetrate the cell membrane and therefore fail to reach their intended intracellular targets

Entrada’s technology leverages endocytic uptake

Through conjugation, our technology enables the intracellular delivery of cargo payloads that are known to be highly active and yet are not cell-permeable on their own

An Entrada biologic consists of a proprietary EEV peptide conjugated to its cargo. The EEV induces effective endocytic uptake of the Entrada biologic into the cell

Entrada’s technology facilitates endosomal escape

After entering the cell, Entrada biologics are initially localized in endosomes. Our unique EEV technology subsequently enables the efficient escape of the conjugated biologics from the endosomes and into the cytosol

In addition to general cytosolic delivery (as illustrated), Entrada biologics can also be engineered to target specific organelles inside the cell

Functional intracellular target engagement

After being released into the cell, the conjugated biologic (e.g., a protein, peptide or oligonucleotide) is able to function normally, access organelles if necessary, engage the intended intracellular target and address the underlying cause of a disease

Publications

Understanding cell penetration of cyclic peptides

  • In: Chem. Rev.
  • By: Dougherty, P., Sahni, A., Pei, D.
View online
2019

Enhancing the cell-permeability of stapled peptides with a cyclic cell-penetrating peptide

  • In: J. Med. Chem.
  • By: Dougherty, P., Wen, J., Pan, X., Koley, A., Ren, J., Sahni, A., Basu, R., Salim, H., Appiah Kubi, G., Qian, Z., Pei, D.
View online
2019

Development of a cell-permeable cyclic peptidyl inhibitor against the Keap1-Nrf2 interaction

  • In: J. Org. Chem.
  • By: Salim, H., Song, J., Sahni, A., Pei, D.
View online
2019

Cyclic cell-penetrating peptides with single hydrophobic groups

  • In: ChemBioChem
  • By: Song, J., Qian, Z., Sahni, A., Chen, K., Pei, D.
View online
2019

Non-peptidic cell-penetrating motifs for mitochondrion-specific cargo delivery

  • In: Angew. Chem. Int. Ed.
  • By: Appiah Kubi, G., Qian, Z., Amiar, S., Sahni, A., Stahelin, R.V., Pei, D.
View online
2018

Cell-permeable bicyclic peptidyl inhibitors against NEMO-IκB kinase interaction directly from a combinatorial library

  • In: J. Am. Chem. Soc.
  • By: Rhodes, C., Dougherty, P., Cooper, J., Qian, Z., Lindert, S., Wang, Q., Pei, D.
View online
2018

Discovery and mechanism of highly efficient cyclic cell-penetrating peptides

  • In: Biochemistry
  • By: Qian, Z., Martyna, A., Hard, R.L., Wang, J., Appiah-Kubi, G., Coss, C., Phelps, M.A., Rossman, J.S., Pei, D.
View online
2016

Early endosomal escape of a cyclic cell-penetrating peptide allows effective cytosolic cargo delivery

  • In: Biochemistry
  • By: Qian, Z., LaRochelle, J.R., Jiang, B., Lian, W., Hard, R.L., Selner N., Luechapanickhul, R., Barrios, A.M., Pei, D.
View online
2014

Efficient delivery of cyclic peptides into mammalian cells with short sequence motifs

  • In: ACS Chem. Biol.
  • By: Qian, Z., Liu, T., Liu, Y., Briesewitz, R., Barrios, A.M., Jhiang, S.M., Pei, D.
View online
2013