Research Interests:

Viral vectors for gene therapy

Viral vectors are very efficient gene transfer tools and are currently being used in many gene therapy trials for the treatment of hereditary disease, infectious diseases and cancer. Long term expression of a transgene often requires integration of the gene into the human genome however random insertion can lead to adverse side effects. We are interested in improving the safety of gene therapy vectors by blocking random integration while retaining effective gene transfer. We have 2 areas of study: 1) We are developing Adeno-associated viral vectors (AAV) that integrate into a specific site within the human genome that is not associated with any pathogenicity. As well as elucidating the mechanism of AAV Rep-mediated integration, we are using this targeted integration strategy to achieve stable transgene expression in dividing cells for gene therapy. 2) Non-integrating lentiviral vectors (NILVs) can be used for stable gene delivery to non-dividing cells. We are currently investigating the use of NILVs to achieve prolonged transgene expression in post-mitotic tissue for the treatment of genetic disease.

Selected Recent Publications:

• Apolonia, L., Waddington, S. N., Fernandes, C., Ward, N., J., Bouma, G., Blundell, M. P., Thrasher, A. J., Collins, M. K., Philpott, N. J. 2007. Stable gene transfer to muscle using non-integrating lentiviral vectors. Molecular Therapy 15(11): p1947-54.

• Philpott, N. J. 2007. Viral vectors for gene therapy - review. In: Encyclopaedia of Life Sciences September. John Wiley & Sons, Ltd: Chichester http://www.els.net/ [DOI: 10.1002/9780470015902.a0020707]

• Philpott, N. J., Thrasher, A. J. 2007. Use of non-integrating lentiviral vectors for gene therapy - review. Human Gene Therapy 18(6) p483-9.

• Schoggins, J. W., Nociari, M., Philpott, N., Falck-Pedersen, E. 2005. Influence of fiber detargeting on adenovirus mediated innate and adaptive immune activation. Journal of Virology 79(18): p11627-37.

• Philpott, N. J., Nociari, M., Elkon, K. B., Falck-Pedersen, E. 2004. Adenovirus-induced maturation of dendritic cells through a PI3 kinase-mediated TNF-alpha induction pathway. PNAS 101(16): p6200-5.

• Philpott, N. J., Gomos, J., Falck-Pedersen, E. 2004. Transgene expression after Rep-mediated site-specific integration into chromosome 19. Human Gene Therapy 15(1): p47-61.

• Cannon, M., Philpott, N. J., Cesarman, E. 2003. The KSHV G protein-coupled receptor has broad signaling effects in primary effusion lymphoma cells. Journal of Virology 77(1): p57-67.

• Philpott, N. J., Gomos, J., Berns, K. I., Falck-Pedersen, E. 2002. A p5 integration efficiency element mediates Rep-dependent integration into AAVS1 at chromosome 19. PNAS 99(19): p12381-5.

• Philpott, N. J., Giraud-Wali, C., Dupuis, C., Gomos, J., Hamilton, H., Berns, K. I., Falck-Pedersen, E. 2002. Efficient integration of recombinant adeno-associated virus DNA vectors requires a p5-rep sequence in cis. Journal of Virology 76(11): p5411-21.

• Trevejo, J., Marino, M., Philpott, N., Josien, R., Richards, E., Elkon, K., Falck-Pedersen, E. 2001. TNF-alpha-dependent maturation of local dendritic cells is critical for activating the adaptive immune response. PNAS 98(21): p12162-7.
  

Last modified on: June 23, 2008