Organ targeting in vivo using phage display peptide libraries.
Preferential homing of tumour cells and leukocytes to specific organs indicates that tissues carry unique marker molecules accessible to circulating cells. Organ-selective address molecules on endothelial surfaces have been identified for lymphocyte homing to various lymphoid organs and to tissues undergoing inflammation, and an endothelial marker responsible for tumour homing to the lungs has also been identified. Here we report a new approach to studying organ-selective targeting based on in vivo screening of random peptide sequences. Peptides capable of mediating selective localization of phage to brain and kidney blood vessels were identified, and showed up to 13-fold selectivity for these organs. One of the peptides displayed by the brain-localizing phage was synthesized and shown to specifically inhibit the localization of the homologous phage into the brain. When coated onto glutaraldehyde-fixed red blood cells, the peptide caused selective localization of intravenously injected cells into the brain. These peptide sequences represent the first step towards identifying selective endothelial markers, which may be useful in targeting cells, drugs and genes into selected tissues.
Pasqualini
R
R
La Jolla Cancer Research Center, The Burnham Institute, California 92037, USA.
Ruoslahti
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001435:Bacteriophages / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D015723:Gene Library; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
D010455:Peptides