|Address:||The Jenner Institute, Old Road Campus Research Building
Roosevelt Drive, Oxford, OX3 7DQ
|Tel:||+44 (0)1865 617625|
|Principal areas of research:||Virology, molecular biology, cell line development|
The main focus of my research is to generate novel cell lines for the growth of replication deficient viral vaccine vectors. Viruses used as vaccine vectors have been engineered to be replication incompetent in host cells. Therefore, these vectors must be grown in either a permissive cell line or complementing cell line. The attenuated pox virus Modified Vaccinia Ankara (MVA) grows in chicken embryo fibroblasts, however these cells contain potentially harmful endogenous retroviruses. Adenovirus vectors which are E1A- require a complementing cell line, such as 293 human embryonic cells, which express E1A proteins.
However, complementing cell lines may result in the generation of recombinant replication competent vectors. Furthermore, the generation of clinical vaccine stocks requires that all cell lines are verified and their origins traceable to ensure a product which is free from retroviruses and TSEs. For some traditionally used cell lines this is a problem. A further limitation to the growth of viral vector stocks is toxicity of the transgene.
Duck cell lines, which do not contain endogenous retroviruses, have been investigated for their ability to support growth of replication incompetent poxviruses. One approach taken to generate GMP cell lines which produce increased yields of adenovirus vectors include engineering complementing cells to express a regulatory element, which inhibits transgene expression during vector growth.
M.G. Cottingham, F. Carroll, S. J. Morris, A. V. Turner, A. M. Vaughan, M. C. Kapulu, S. Colloca, L. Siani, S. C. Gilbert and A. V. S. Hill. (2012) Preventing spontaneous genetic rearrangements in the transgene cassettes of adenovirus vectors. Biotechnology and Bioengineering http://onlinelibrary.wiley.com/doi/10.1002/bit.24342/pdf
Morris, S. J., D. C. Farley and K. N. Leppard (2010) Generation of cell lines to complement adenovirus vectors using recombination mediated cassette exchange. BMC Biotechnology 10:92