Introduction

Development of nucleotide sequences coming from Stabilina2 for the gene expression regulation of FVIII in specific human cells, for the Hemophilia A care. This genetic disease is associated to deficit or reduction of FVIII activity of the coagulation. This gene therapy of viral vector represents a promising alternative to the current FVIII substituted products, thank to its low collateral effect.

Technical features

The developed nucleotide sequences coming from Stabilin2 promoter were demonstrated effective in the Hemophilia A treatment, through gene therapy. When these sequences are exploited for expression regulation of the FVIII, lead to the long-term care of disease, without collateral effects, limiting the expression in the sinusoidal liver cells, naturally producting of FVIII. In particular, the laboratory experimentation on hemophilic cavies demonstrates the production of high and constant therapeutic levels of FVIII (with 10-11% activity). The Stabilina2 promoter shows higher results with respect to previous patented FVIII promoter. These results lead to new, safe and  effective gene and cellular therapy strategies, exploitable for the care either of coagulation disease or other genetic defects pathologies.

Possible Applications

• Cellular and gene therapy of the Hemophilia A;
• Physiologically regulated espression of recombinant and/or therapeutic proteins in specific cells.

Advantages

• Stabilina2 promoter is selective for the sinusoidal endothelial cells of liver;
• Long lasting and physiologic expression of FVIII and/or other therapeutic proteins;
• Limited/absence immunity response versus expressed protein.