Uptake and processing of modified bacteriophage M13 in mice: implications for phage display.
Internalization and degradation of filamentous bacteriophage M13 by a specific target cell may have major consequences for the recovery of phage in in vivo biopanning of phage libraries. Therefore, we investigated the pharmacokinetics and processing of native and receptor-targeted phage in mice. (35)S-radiolabeled M13 was chemically modified by conjugation of either galactose (lacM13) or succinic acid groups (sucM13) to the coat protein of the phage to stimulate uptake by galactose recognizing hepatic receptors and scavenger receptors, respectively. Receptor-mediated endocytosis of modified phage reduced the plasma half-life of native M13 (t(1/2) = 4.5 h) to 18 min for lactosylated and 1.5 min for succinylated bacterophage. Internalization of sucM13 was complete within 30 min after injection and resulted in up to 5000-fold reduction of bioactive phage within 90 min. In conclusion, these data provide information on the in vivo behavior of wild-type and receptor-targeted M13, which has important implications for future in vivo phage display experiments and for the potential use of M13 as a viral gene delivery vehicle.
Molenaar
Tom J M
TJ
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Sylvius Laboratory, 2300 RA Leiden, The Netherlands.
Michon
Ingrid
I
de Haas
Sonja A M
SA
van Berkel
Theo J C
TJ
Kuiper
Johan
J
Biessen
Erik A L
EA
D000818:Animals; D017104:Bacteriophage M13 / Q000502:physiology*; D004705:Endocytosis; D015316:Genetic Therapy; D008099:Liver / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D019151:Peptide Library
D019151:Peptide Library