Novel MVA mutant eliciting enhanced T cell memory

Reference Number TO 01-00355

 

Challenge

Vectors of viral origin are often used in gene therapy in order to introduce foreign genetic information into eukaryotic recipient cells. At present, no vector system possesses all characteristics necessary or desirable in an ideal gene delivery system, but Epstein-Barr virus (EBV)-derived vectors overcome several of the problems associated with other viral vector systems. The establishment of latent infections in its target cells sustains long-term persistence of EBV viral genomes in vivo. Both latent infection and non-integrating, episomal maintenance are advantageous features for gene therapy. Vectors derived from herpes viruses or other large DNA viruses require a helper cell line for vector encapsidation to provide the necessary factors in trans. The packaging cells are infected with a mutant virus that complements for those functions the gene vector lacks. As a consequence, both the encapsidated vector and the helper virus are released, which is a major drawback. 

 

  

 

Technology 
To overcome this intrinsic problem, the invention describes the preparation of EBV gene vectors, advantageous in that a helper cell line has been constructed and is used which does not release any helper viruses during the packaging of gene vectors. The cell line carries an EBV mutant that is devoid of its terminal repeats (TRs), which prevents packaging of its DNA into virions. The EBV mutant genome is capable of encapsidating foreign DNA that carries the TR-packaging signals. Moreover, this novel helper cell line encapsidates EBV-derived plasmids with an 10 times higher efficiency than previously used cell lines.

Commercial Benefit

This packaging cell line can be used to deliver any gene of interest into primary B cells or established B-cell lines. The packaging cell line and the recombinant EBV vectors may be used in gene transfer into human cells providing a suitable tool for in vivo applications in human gene therapy.

Developmental Status
An optimized helper-virus free packaging cell line which harbors an EBV helper virus genome with specific genetic alterations has been generated. In addition, a novel gene vector plasmid devoid of prokaryotic antibiotic resistance genes has been constructed. 

Patent Situation
Patents are granted in the US (US 6,436,693), EU (EP0915165), and Australia (AU0747763).

Commercial Opportunity
License is being offered on an exclusive or non-exclusive basis. In addition, cooperation can be offered and will be strongly desired.

Relevant Publication
Delecluse et al. (1999), Proc. Natl. Acad. Sci. USA 96, 5188-5193; Wendtner et al. (2003), Exp. Hematol. 31, 99-108; Hettich et al. (2006), Gene Therapy 13, 844-856.

 

 

 

 

 

 

Download als PDF 

 

Contact:

Hubert Müller, Ph.D.
Technology Manager
Ascenion GmbH

T: +49 (0)89 318814-32
F: +49 (0)89 318814-20
mueller@ascenion.de