Peptide-mediated targeting of hepatocytes via low density lipoprotein receptor-related protein (LRP).
It has previously been reported that a peptide sequence of T7 phage protein p17 mediates uptake of its cargo by liver parenchymal cells. The aim of this study was to identify the phage-binding receptor. The involvement of LRP was confirmed by the observations that phage binding to Hepa 1c1c7 cells was inhibited by the LRP-binding receptor-associated protein, LRP-deficient mouse embryonic fibroblasts bound phage with lower efficiency than their wild-type counterparts, and using mouse models with ablated LRP liver expression. The identification of LRP as a cognate receptor for this sequence offers a new ligand-receptor combination for hepatocyte delivery of therapeutic agents.
Ludtke
James J
JJ
Waisman Center, Departments of Pediatrics and Medical Genetics, University of Wisconsin-Madison, Madison, WI 53705, USA.
Sokoloff
Alex V
AV
Wong
So
S
Zhang
Guofeng
G
Strickland
Dudley K
DK
Wolff
Jon A
JA
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides; D000818:Animals; D017123:Bacteriophage T7 / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding
D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010455:Peptides