Our RNAi therapies will be universal for all diseases caused by CAG repeats expansions (polyglutamine diseases) including: Huntington’s disease, Spinocerebellar ataxias, Dentatorubral Pallidoluysian Atrophy (DRPLA) or Spinal & Bulbar Muscular Atrophy (SBMA, Kennedy disease).
In DYST 201 (Huntington’s disease therapy) interfering RNAs are designed to target directly the CAG repeat tract. Specific modifications of their sequence result in formation of mismatches between interfering RNA and a target transcript. Typical normal huntingtin transcript binds a single RISC, whereas the mutant variant binds more silencing complexes. During protein synthesis, the mismatched RISC from normal transcripts is easily depleted in contrast to the multiple RISCs on the mutant transcripts, which are stable and inhibit translation. This lead to allele-selective inhibition of mutant huntingtin synthesis. The degree of selectivity depends on the difference in length between the repeat tracts in the normal and mutant alleles.
Application of Dystrogen Therapeutics proprietary vectors and promoters gives the possibility to regulate expression of interfering RNA of shRNA- and sh-miR-type, their selective delivery to the tissues of interest and most importantly a long-term silencing effect.
Our novel RNAi therapy will bring the long-term silencing effect of the mutated gene and therefore will inhibit the progress of neurodegenerative diseases caused by a toxic protein produced by CAG repeats.