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Development of an episomal vector system for human gene therapy


Foreseen Results

We believe that the proposed research will allow us to develop novel gene therapy vectors which will be compatible with Therexsys' novel non-viral delivery systems. These technologies will have the potential for use in development of a wide range of new therapies, including vaccines, treatments for cancer, inherited disorders and infections.
We describe a program of research to develop improved papillomavirus-based vectors for applications in human gene therapy. An episomal expression vector comprising the BPV-1 E1 cis-acting replication sequences and the trans-acting E1 and E2 genes has been developed. The BPV-1 system has been shown to replicate autonomously to a level of 30 copies per cell, and is stably maintained and expressed in a wide range of mammalian cells including human cell lines. We now propose to undertake the following program of improvements which we believe will make this vector system substantially more suitable for use in human gene therapy:

1. Further characterisation of the prototype vector to determine the breadth of cell types capable of supporting stable replication.
2. Construction and evaluation of vectors containing tissue-specific and small molecule-regulated regulatory elements controlling expression of viral replication proteins.
3. Analysis and attenuation of non-replicative activities of BPV-1 E2.
4. Analysis and attenuation of BPV-1 E1 and E2 immunogenicity, to ensure that therapeutic vectors have minimal immunogenicity.
5. Evaluation of vectors with novel non-viral delivery systems. Therexsys' non-viral gene delivery systems will be used to study maintenance of the episomal vectors described in this proposal in both cell lines and laboratory animals. A range of cell-specific, targeted delivery systems and a series of high efficiency, non-targeted delivery systems will be used to define the range of body tissues in which these vectors can be maintained when administered systemically to mice via the tail vein.

Funding Scheme

CSC - Cost-sharing contracts


Stephenson Building, Science Park, Keele
ST5 5SP Newcastle
United Kingdom

Participants (3)

Erasmus Universiteit Rotterdam
50,Dr. Molewaterplein
3000 DR Rotterdam
Estonian Biocentre
23,Riia Street
2400 Tartu
1A7,lenkkeilijankatu 8
33520 Tampere