Wisconsin Alumni Research Foundation

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A Non-Cytotoxic oriP/EBNA-1 Vector for Human Gene Therapy
WARF: P04170US

Inventors: William Sugden, Gregory Kennedy, Jindong Wang

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing a non-cytotoxic EBNA-1 derivative that supports extrachromosomal replication of oriP.
Overview
The Epstein-Barr virus (EBV) is a member of the Herpes family of viruses.  The EBV origin of plasmid synthesis, oriP, efficiently supports DNA synthesis in higher eukaryotic cells.  This origin uses only one viral protein, EBNA-1.  All other factors are provided by the cell. 

The oriP/EBNA-1 vector has been a popular cell culture tool for the expression of DNA sequences of interest.  Vectors derived from EBNA-1 also are being considered for use in gene therapy.  However, EBNA-1 is cytotoxic when overexpressed in a cell and also may be oncogenic.
The Invention
UW-Madison researchers have developed a vector encoding a derivative of EBNA-1 that is not cytotoxic when expressed efficiently in cells.  The derivative lacks several amino acids from the LR1 region.  It supports extrachromosomal replication, maintenance and transcription from extrachromosomal oriP-containing vectors, but does not substantially activate expression of host cell genes. 
Applications
  • Gene therapy
Key Benefits
  • Useful in vitro or in vivo
  • Will not kill host cells when expressed at high levels
  • May be used to deliver genes to tumor cells
  • May be used with many cell types in cell culture
  • Avoids insertional mutagenesis by maintaining DNA as plasmids
Additional Information
For More Information About the Inventors
Publications
  • Kennedy G. and Sugden B. 2003. EBNA-1, a Bifunctional Transcriptional Activator.
For current licensing status, please contact Rafael Diaz at [javascript protected email address] or 608-960-9847

WARF