Universität Autonoma De Barcelona

Other

Fundación Del Sector Público Estatal Centro Nacional De Investigaciones Oncologicas Carlos III (f.s.p. Cnio)

Fatima Bosch Tubert

Maria Bobadilla

Veronica Jimenez Cenzano

Eduard Ayuso Lopez

Verónica Jiménez Cenzano

Maria Antonia Blasco Marhuenda

Alfons Valera Abril

Cristina Mallol Dominguez

Miguel Garcia Martinez

Veronica Jiménez Cenzano

Virginia Haurigot Mendonça

Miquel Garcia Martinez

Virginia Haurigot Mendoca

Albert Ruzo Matias

David Callejas Castineiras

Christian Baer

Ivan Formentini

They are provided gene constructs comprising a nucleotide sequence encoding the Insulin-like growth factor 1 (IGF-1) of a mammal; and target sequences of a microRNA of a tissue where the expression of IGF-1 is wanted to be prevented, wherein the sequences (a) and (b) are operationally linked to a promoter of ubiquitous expression. Also provided are expression vectors comprising the gene construct and pharmaceutical compositions comprising them. They are useful in the treatment and/or prevention of diabetes mellitus in mammals, wherein a dysfunction and/or a loss of the beta-cells of the islets of Langerhans is present.

Viral vectors for the treatment of diabetes

The invention relates to a viral expression construct and related viral vector and composition and to their use wherein the construct and vector comprise elements a) and b): a) a nucleotide sequence encoding an insulin operably linked to a first promoter, b) a nucleotide sequence encoding a glucokinase operably linked to a second promoter and the viral expression construct and related viral vector comprise at least one of elements c), d) and e): c) the first and the second promoters are positioned in reverse orientation within the expression construct, d) the first and the second promoters are positioned in reverse orientation within the expression construct and are located adjacent to each other and e) the first promoter is a CMV promoter, preferably a mini CMV promoter.

Single-vector gene construct comprising insulin and glucokinase genes

The chimeric gene is directed by a promoter or fusion of promoters which preferably are regulable and activated by the diabetic process. Preferably, it is obtained by fusion of the human insulin gene to the promoter of PEPCK (P-enolpiruvate carboxiquinasa). Said promoter (fragment &minus;460 bp to &plus;73 bp) is fused to the flank zone of the human insulin gene (&minus;170 bp to &plus;1). The gene of the human insulin contains two coding exons E1 and E2 and two introns A and B. It also relates to an expression vector which allows the expression of insulin in cells which are different from the &bgr;-cells of the pancreas, and to a transgenic animal which expresses said chimeric gene. It is especially used for the gene therapy of diabetes.

Chimeric gene using the gene or cDNA of insulin, specially for the gene therapy of diabetes

PEPCK-insulin gene construct and transgenic mouse

Growing community of inventors

Cerdanyola del Valles, Spain

Fatima Bosch Tubert