Introduction

We used the “Zinc-Finger Artificial Transcription Factors ZF-ATFs” technology to reprogram the expression of genes related to rare diseases. We combined ZF-ATF technology with adeno-associated viral vector technology to develop gene therapy projects related to muscular dystrophies such as Duchenne muscular dystrophy (DMD).

Technical features

The therapeutic strategy we propose for Duchenne Muscular Dystrophy (DMD) is based on artificial transcription factors Zinc Finger (ZF-ATF), addresed to the “A” promoter of the utrophin gene to up-regulate its expression. The main advantages of our ZF-ATFs over other the current gene therapy technologies for DMD are; i) ZF-ATFs are applicable to all DMD patients regardless of the type of mutation present in Dystrophin; ii) ZF-ATFs are active at low concentrations and due to their small size they are ideal in gene therapy; iii) ZF-ATFs are a valid alternative to the replacement of large mutated genes; iv) ZF-ATFs mimic the natural mechanism of transcription regulation, producing all the “isoforms” of the target gene product; and v) Our ZF-ATFs are designed to avoid/reduce any immune response.

Possible Applications

• ZF-ATFs on promoters of “beneficial or mutated” target genes allow to positively or negatively regulate the expression of these genes with unlimited therapeutic purposes;
• The combination of ZF-ATF and adeno-associated vector technologies is applicable to both genetic and viral pathologies.

Advantages

• ZF-ATF are applicable to all DMD mutations;
• ZF-ATFs are active at low concentrations;
• Reduced dimensions of ZF-ATFs is ideal for the use for AAV viral vectors;
• ZF-ATF genes mimic the natural mechanism of gene transcription regulation;
• ZF-ATFs show very low immunogenicity.