Organ targeting In vivo using phage display peptide libraries

R Pasqualini, E Ruoslahti - Nature, 1996 - nature.com
R Pasqualini, E Ruoslahti
Nature, 1996nature.com
PREFERENTIAL homing of tumour cells1, 2 and leukocytes3, 4 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 inflammation5–8, and an endothelial
marker responsible for tumour homing to the lungs has also been identified9. Here we report
a new approach to studying organ-selective targeting based on in vivo screening of random …
Abstract
PREFERENTIAL homing of tumour cells1,2 and leukocytes3,4 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 inflammation5–8, and an endothelial marker responsible for tumour homing to the lungs has also been identified9. Here we report a new approach to studying organ-selective targeting based on in vivoscreening 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.
nature.com