Abstract: The present invention relates to an enhanced and simplified herpes virus amplicon packaging system. The packaging system comprises a herpes virus amplicon vector and a packaging vector. In one embodiment, the packaging vector comprises a bacterial artificial chromosome (BAC) containing the HSV-1 genome. The packaging vector contains an intact pac site but is otherwise rendered packaging defective. The packaging vector can be rendered packaging defective by inserting nucleotides into the pac site, or by otherwise interfering with the capsid's ability to close, for example, by increasing the size of the DNA fragment upon which the herpes virus genome is cloned. This system can be used to package a wide range of nucleotide sequences (e.g., a therapeutic or antigenic gene) into an empty herpes virus particle taking advantage of the large transgene capacity of herpes viruses. This system can also be used as a vaccine to induce protective immunity against HSV-1, or other complex pathogens.
Type:
Grant
Filed:
December 9, 1999
Date of Patent:
June 3, 2003
Assignees:
The General Hospital Corporation, University Medical Centre St. Radboud of the University of
Nijmegen, University of Zurich, The Walter & Eliza Hall Institute of Medical
Research
Inventors:
Xandra O. Breakefield, E. Antonio Chiocca, Yoshinaga Saeki, Cornel Fraefel, Kurt Tobler, Mathias Ackermann, Mark Suter, Gosse J. Adema, Ken Shortman