This month’s lab-profile introduces Dr Richard Harbottle, a Research Fellow at the National Heart and Lung Institute at Imperial College London. Dr Harbottle heads the Gene Therapy research group at Imperial College and is studying gene therapy as a potential treatment for BHD syndrome. Dr Harbottle is a founding member of the British Society for Gene Therapy and he is also a member of the American and European Gene Therapy Societies.
Gene therapy involves the insertion of genetic material into a cell to correct for a mutated or deleted gene. The genetic material is delivered to a cell using a vector, which contains the desired gene along with all the additional elements needed for gene expression. The biggest challenge in gene therapy is delivery of the gene construct to the cells and maintaining appropriate levels of expression of the inserted gene.
The most effective gene delivery systems to be developed are based around viruses, due to their ability to insert genetic material into a host cell. However, Dr Harbottle and his research associate Dr Suet-Ping Wong are developing non-viral methods of gene therapy in the hope that these methods will be less toxic and more versatile.
Dr Harbottle and Dr Wong have developed a non-viral S-MAR plasmid vector which replicates episomally in vivo (Wong et al., 2011a). The vector has successfully been used to insert the Bcl-2 gene into the liver of mice and expression was observed for over 3 months (Wong et al., 2011a).
The Gene Therapy lab at Imperial College is now trying to apply this technique to BHD syndrome, by constructing vectors which contain FLCN. The hope is that these vectors can be delivered to the kidneys, or to skin and lung cells, of BHD patients to overcome the symptoms caused by the mutated FLCN gene.
To learn more about Dr Harbottle and Dr Wong’s on-going BHD research, watch the video interview available on BHDsyndrome.org, along with the accompanying audio-only and written transcript files. The following publications may also be of interest:
- Wong SP, Argyros O, Coutelle C, Harbottle RP. Non-viral S/MAR vectors replicate episomally in vivo when provided with a selective advantage. Gene Therapy. 2011a Jan;18(1):82-7. PMID:20739959
- Wong SP, Argyros O, Howe SJ, Harbottle RP. Systemic gene transfer of polyethylenimine (PEI)-plasmid DNA complexes to neonatal mice. J Control Release. 2011b Mar 30;150(3):298-306. PMID:21192993
- Argyros O, Wong SP, Fedonidis C, Tolmachov O, Waddington SN, Howe SJ, Niceta M, Coutelle C, Harbottle RP. Development of S/MAR minicircles for enhanced and persistent transgene expression in the mouse liver. J Mol Med. 2011 May;89(5):515-29. PMID:21301798
www.bhdsyndrome.org – the primary online resource for anyone interested in BHD Syndrome.