HOUSTON - Scientists who developed a technology for identifying and targeting unique protein receptor ZIP Codes on the cellular surface have found a way to penetrate the outer membrane and deliver engineered particles - called iPhage - to organelles inside the cell.
In a paper published today online in Nature Communications, the team led by researchers at The University of Texas MD Anderson Cancer Center reports packaging the phage particles with a peptide called penetratin to reach inside the cell.
This new capacity was used to screen for peptide ligands - binding agents - that connect to receptors on mitochondria, which generate a cell's energy, and ribosomes, which process mRNA to make proteins.
The team found a peptide that binds to a specific ribosomal protein called RPL29 which, when delivered with penetratin, disrupts ribosomal function and kills cells. Cell survival was reduced in both malignant and non-malignant cells and in both mouse and human cell lines.
"We provided proof-of-concept for a direct intracellular ligand-receptor screening technology, which is clearly an unmet need in cancer biology, along with the discovery of an organelle ZIP Code that mediates cell death," said Renata Pasqualini, Ph.D., co-senior author of the paper and a professor in MD Anderson's David H. Koch Center for Applied Research of Genitourinary Cancers.
The RPL29 pathway is a new cell death pathway. The researchers found evidence of three types of cell death caused by disrupting the pathway with the new ligand.
"The molecular tool reported here along with its future ramifications will hopefully be of interest to targeted drug development, gene delivery, and mechanisms of human organelle diseases," said Wadih Arap, M.D., Ph.D., also of the Koch Center.
The iPhage screens for ligands inside the cell
Arap and Pasqualini pioneered a screening technique that exploits the existence of unique
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center