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Development of more efficient and safer expression vectors for gene therapies

This project aims at constructing genetic vectors mediating more efficient expression of therapeutic genes for safer gene and cell therapies.

Safe and efficient somatic gene therapies may demand tight regulation of transgene expression in the patient, using medically acceptable drugs. For this purpose, we constructed expression vectors where transgene expression is regulated by a genetic network of engineered activators and silencers of transcription. We are also identifying and evaluating genetic insulator elements that may prevent the interactions of the vector with cellular genes, so as to increase the effectiveness of therapy and reduce the risk of harmful side effects for the patient, using either non-viral or viral vectors.

Our work has enabled the identification of small genetic insulator elements that may be incorporated into retroviral and lentiviral vectors used in human gene therapy. These elements block the accidental activation of cellular genes by regulatory sequences present on the therapeutic vector and they stabilize the expression of therapeutic genes. This work has been supported by the European Network of Excellence in Gene Therapy (CLINIGENE Network of Excellence), and collaborations with other network members have demonstrated significant improvement in the safety and efficacy of some prospective gene therapy vectors.
 

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Transversal slice of mouse muscle electrotransferred with a plasmid expressing the Green Fluorescent Protein-GFP.
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