NUCLEIC ACID PRECISION THERAPY FOR TANDEM-REPEAT DISEASES

The research project focuses on precision medicine; therapeutic oligonucleotides (ONs).

Our unique niche is to develop anti-gene ONs (A-GOs), which bind to the DNA duplex, where our strategy is world-leading.

We found that A-GOs binding to the disease gene in tandem repeat-expansion disorders (TREDs), such as Huntington’s disease (HD) and Friedreich’s ataxia (FRDA), significantly modulates gene expression.

The fact that A-GOs binding within the chromatin down-regulates the expression of Huntingtin in patient cells, is by all criteria a breakthrough.

Also, our recent findings demonstrate that specifically designed A-GOs not only revert the gene silencing in FRDA but also block the repeat expansion in mammalian cells. In other words, for the first time we can target the root cause of these diseases, the repeat expansion itself.

Moreover, our accumulated expertise in nucleic acid therapeutics for genetic diseases has an evident added-value to the development of additional gene-therapies, such as gene editing.

We aim to move our precision medicine ONs closer to the clinics focusing on the following:Advance our A-GOs therapeutic concept for FRDA and HD by studying their effect in patient-derived cells, differentiated iPS cells, and in animal models with focus on disease prevention and treatment.Develop FRDA gene therapy based on an in-house minicircle technology.Study the mechanisms underlying repeat expansions in FRDA and HD and in the novel TRED named CANVAS.