Dendritic Cells and Lentiviral Vectors: Mapping the Way to Successful Immuno Gene Therapy
By Cleo Goyvaerts, Grazyna Kochan, David Escors and Karine Breckpot
- Prof. David Escors
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- I started working on coronavirus structure and morphogenesis in 1997 as my PhD project. As a result, a novel structural model for coronavirus was proposed. During my predoctoral work I had also experience working with several virus systems, including a biosecurity P-3 human pathogen, the endemic balkan nephropathy-associated virus. After my PhD thesis, I continued in Prof. Enjuanesâ€™ laboratory as a post-doctoral researcher, in which a new generation of vectors based on the coronavirus genome are being developed for human and animal gene therapy and vaccination. As the result of these investigations, a new replication-competent, propagation-deficient coronavirus vector has been engineered by reverse genetics. Additionally, the TGEV packaging signal was localised to study the molecular mechanisms of coronavirus packaging and generate biosafe suicide vectors as an additional security measure for application in humans. The phosphorylation of coronavirus nucleocapsid protein was studied and its implication in the regulation of coronavirus replication, transcription and assembly was addressed. Finally, I additionally worked in the engineering of a SARS-CoV infectious cDNA clone. After my first post-doctoral position in Prof. Enjuanesâ€™ research group, I moved to Prof. Collinsâ€™ laboratory as a Senior Research Fellow in the Windeyer Institute, University College of London. The research at UCL is focused on the characterization of the molecular mechanisms of dendritic cell function. We have determined the intracellular signalling pathways controlling DC function, in order to induce effective immune responses or tolerance for specific antigens. This knowledge is currently being applied for the development of effective immunisation protocols using lentivectors to overcome tumour-induced tolerance. After my second post-doctoral position in Prof. Collinsâ€™ research group, I set up an independent research group dedicated to the molecular and cellular mechanisms of immunological tolerance by genetic modification of dendritic cells using lentiviral vectors.
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