Development and characterisation of improved materials derived from human adenoviruses to be used in gene therapy (LGN.3977)

Gene therapy aims at introducing genetic material into cells of patients to accomplish a therapeutic effect. For that purpose both viral and non-viral gene-delivery systems are being exploited as methods to package genetic material and introduce it into the cell. Sofar, replication-defective recombinant viruses prove to be more efficient than non-viral systems. An advantage of using recoinbinant adenoviruses (recAd) is that they can be used in vivo to accomplish efficient gene delivery to a wide variety of target cells. Since it is generally accepted in the field that in-vivo gene transfer will become more important than ex-vivo applications, recAds are promising vehicles for a broad array of clinical gene therapy studies.
The recAds currently available have some disadvantages that hamper their clinical application:

1. The generation of Replication-Competent Adenovirus (RCA) during recAd production,
2. the toxicity of recAd-vectors, and
3. the laboratory methods used for propagation and purification of recAds are not suitable for production of batches of the quality and quantity necessary.

These problems are interrelated and should all be solved in order to exploit RecAd-technology commercially. The research programme addresses all three issues: We will generate new, safe packaging cell lines for the production of recAds, decrease the toxicity of recAds by deleting a larger part of the adenovirus genome from the recAd-vector and acquire the technology for large-scale production of clinical grade recads. This will not only strengthen our position in the gene-therapy field by making possible the large-scale production of superior vectors, but its spin-off will help other groups in the Netherlands (and abroad) by the availability of the tools to develop and produce safe recAd-vectors for a variety of applications.

Eén bedrijf is bij dit project betrokken.

Prof.dr. D. Valerio
Universiteit Leiden
Faculteit Geneeskunde
Vakgroep Medische Biochemie
Medisch Genetisch Centrum Z/W NL
Postbus 3271
2280 GG RIJSWIJK.