Enhanced packaging of herpes virus amplicons and generation of recombinant virus vectors

US6573090B1 · kind B1 · utility

Assignees

• The General Hospital Corporation · US
• University Medical Centre St. Radboud of the University of Nijmegen · NL
• Universitat Zurich · CH
• THE WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH · AU

Inventors

• Xandra O. Breakefield · Newton, US
• E. Antonio Chiocca · Wakefield, US
• Yoshinaga Saeki · Toyama, JP
• Cornel Fraefel · Frauenfeld, CH
• Kurt Tobler · Chur, CH
• Mathias Ackermann · Bassersdorf, CH
• Mark Suter · Luzern, CH
• Gosse Jan Adema · Nijmegen, NL
• Ken Shortman · Queenstown, AU

Key dates

• Filing date: Dec 9, 1999
• Grant date: Jun 3, 2003
• Expiry date: Dec 9, 2019

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2800/204
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

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.