BrainVectors IAPP


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       BrainVectors is a network of public and private sector research institutions, which aims devising new gene therapy (GT)-based treatments for Parkinson’s disease (PD), by delivering GDNF into the CNS with vectors derived from adeno-associated (AAV), canine adenoviruses (CAV-2) and lentiviruses (LV). Although AAV, CAV-2 and LVV vectors have acceptable bio-safety, their immune response must be better characterized to develop these vectors for clinical use. The possibility to regulate gene expression by inducible promoters represents a significant pharmacological progress of the gene therapy approach for PD. Therefore the work of this consortium will:

▪ identify inducible gene expression cassettes with increased sensitivity of transactivators and inducers, will reducing the dose of drugs necessary to obtain GDNF expression;

▪ characterize the immune responses induced by the components of GDNF-AAV, -CAV-2 and -LVV in rodent models for PD by using biomarker-based immunological screening.

         The project is based upon a network of 11 academic, private non-profit organizations and SMEs. Some partners are committed in developing vectors backbones, vector production technologies and PD animal models. Others have strong immunological background, pioneering the biomarkers-based immuno-technologies for GT vectors, and have R&D expertise/facilities in/for animal cell technologies cGMP for biopharmaceuticals.

        26 researchers will be involved during the 48 months of the research activities and transfer of knowledge, with an intense program of visits (secondments) between academic institutions and SMEs. Among these researchers, who are mainly the staff of the partner institutions, 3 newly recruited post-docs will be involved.

            The BrainVectors IAPP will be in tight connection with other EC-funded consortiums, e.g. the ADVance ITN, in order to amplify the transfer of knowledge and technology within the ERA and to increase the career opportunities for the young researchers.


Workshop in Lausanne on 12th- 14thSeptember, 2016


Publications related to the scientific context of BrainVectors:

Optimization of the Tet-On system for regulated gene expression through viral evolutionX Zhou, M Vink, B Klaver, B Berkhout and AT Das Gene Therapy, 2006, 19:1382-90 (download the pdf)


A Sensitive Cell-Based Assay to Measure the DoxycyclineConcentration in Biological Samples Wendy Kleibeuker, Xue Zhou, Mireille Centlivre, Nicolas Legrand,  Mark Page,  Neil Almond, Ben Berkhout,  and Atze T. Das  Human Gene Therapy, 2009, 20:524–530 (download the pdf)


 Development of a liver specific Tet-On inducible system for AAV vectors  Vanrell, L., M. di Scala, L. Blanco, I. Otano, V. Baldim, A. Paneda, P. Berraondo, S. Beattie, P. Alzuguren, R. Hernandez, A. Chtarto, L. Tenenbaum, J. Prieto, G. Gonzalez-Aseguinolaza.   Molecular Therapy, 2011, 19:1245-53 (download the pdf)


How can measurement, monitoring, modeling and control advance cell culture in industrial biotechnology?  Manuel J. T. Carrondo, Paula M. Alves,, Nuno Carinhas, Jarka Glassey, Friedemann Hesse, Otto-Wilhelm Merten, Martina Micheletti, Thomas Noll, Rui Oliveira, Udo Reichl, Arne Staby, Ana P. Teixeira, Henry Weichert and Carl-Fredrik Mandenius    -    Biotechnol. J. 2012, 7, 1522–1529 (download the pdf)

A next step in adeno-associated virus (AAV)- mediated gene therapy for neurological diseases: Regulation and targeting.  Chtarto, A., Bockstael, O., Tshibangu, T., Dewitte, O., Levivier, M. and Tenenbaum, L. British Journal of Clinical Pharmacology 2013, 76: 217–232 (download the pdf)

An adeno-associated virus-based intracellular sensor of pathological Nuclear Factor-kappa B activation for disease-inducible gene transfer  Chtarto, A., Bockstael, O., Gebara, E., Vermoesen, K., Melas, C., Pythoud, C., Levivier, M., Dewitte, O., Luthi-Carter, R., Clinkers, R. and Tenenbaum L. PlosOne 2013; 8(1): e53156  (download the pdf)

Functional Neuroprotection and Efficient Regulation of GDNF Using Destabilizing Domains in a Rodent Model of Parkinson’s Disease     Luis Quintino, Giuseppe Manfré, Erika Elgstrand Wettergren, Angrit Namislo, Christina Isaksson  and   Cecilia Lundberg. Mol Ther. 2013 Jul 24. doi: 10.1038/mt.2013.169(download the pdf)



Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9 Malin Åkerblom, Rohit Sachdeva, Luis Quintino, Erika Elgstrand Wettergren, Katie Z. Chapman, Giuseppe Manfre, Olle Lindvall, Cecilia Lundberg  & Johan Jakobsson. Nature Communications 2013 | 4:1770 | DOI: 10.1038/ncomms 2801 (download the pdf)