Non-specific translocation of peptide-displaying bacteriophage particles across the gastrointestinal barrier

Abstract

Phage display technology Could provide a rapid means for the discovery of novel peptides and proteins from genetically engineered variants which may act as specific vehicles for drug delivery particularly through the intestinal barrier. In this work, we utilized in vivo phage display in order to Study the sequences which may be responsible for transmucosal transport. We hypothesized that the introduction of a library of peptide displaying phages into the intestine may lead to the identification of sequences that Could induce transport. A biopanning protocol was performed by applying a 7-mer random amino acid phage library to mice by gavage and then assessing their absorption via phage recovery from the spleen and blood. Following the isolation of 77 different phages, the sequences of the displayed peptides were identified. Statistical treatment of the obtained sequences did not support the notion that the GI trams-location depends on the presence of any particular peptide sequence fused on the pIII coat proteins of the M 13 phages. There are, however, some residue types underrepresented which could be due to specific GI selection mechanisms and/or their effects on the amplification rate for phages bearing those residues. (C) 2008 Elsevier B.V. All rights reserved.