DREJA HANNA · Engineering of vesicular stomatitis virus-g protein (vsv-g) to retarget recombinant infectious viral particles

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Project objective

Gene therapy has the potential to become a future medical choice for treatment of many diseases, ranging from monogenetic disorders to cancers and autoimmunity. However, before gene therapy will be clinically successful and widely available, there are numerous obstacles to overcome and many further improvements to be made. One of the most urgent objectives is to generate high levels of transgene products at the site of interest, hence intensifying the local effect whilst reducing unwanted reactions associated with inappropriate distribution of the recombinant protein. A viable approach issuing a targeted infection strategy where viral vectors are supplied in vivo. To date, Env of Moloney murine leukemia virus (MoMLV) has been engineered to express modified specificities, although these alterations have been associated with a lack of efficient infection levels. Interestingly, VSV-G, a commonly used pseudo typing protein, which exceeds MoMLV Env in both stability and fusogenicity, has been overlooked in the attempts to obtain targeted vectors. The binding and fusion domains of VSV-G remain unidentified, which may be a reason for this oversight. We are thus interested in characterizing both these regions of VSV-G. Ultimately, we are aiming at modifying the protein to acquire a different retroviral vector specificity. If successful, these findings may significantly complement today's attempts to realize the prophecy of gene therapy. Targeted gene delivery interests me immensely, hence I contacted Dr Piechaczyk regarding continuing my post-doctoral training with his group, as they possess extensive expertise in the area. The opportunity to carry out research in this field, at this level, did not appear very probable if I had returned to Sweden. I have very much enjoyed the different experiences obtained by working in laboratories in the UK, Ireland and Sweden (the latter two during my undergraduate studies), thus looking for a laboratory in another European country was a very interesting proposition. As I have had the pleasure to encounter in recent months, independent scientific exploration is encouraged in the group. This combination gives the ultimate milieu for any scientist, wishing to develop and gain experience for a future career in research. Practically, there are a number of new techniques to master, such as development and handling of viral vectors. Moreover, the possibility to be in full command of another European language is yet a reason for me wishing to remain in France. With my strong background in immunology and molecular biology, I believe that I complement the group well.

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Participants

• CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE · PARISCoordinatorFrance

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