Oligonucleotide-based strategies to combat polyglutamine diseases.
Bottom Line: The latter include targeting SNP variants associated with mutations or targeting the pathologically expanded CAG repeat directly.We compare gene silencing effectors of various types in a number of aspects, including their design, efficiency in cell culture experiments and pre-clinical testing.We discuss advantages, current limitations and perspectives of various ON-based strategies used to treat polyQ diseases.
Affiliation: Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.Show MeSH
Related in: MedlinePlus
Mentions: In the traditional view of gene expression, the expanded CAG*CTG repeats present in mutant polyQ disease genes are transcribed into CAG repeats in RNA and translated into polyQ tracts in the encoded proteins (Figure 1). The abnormal protein–protein interactions triggered by mutant proteins were long thought to be the only factor responsible for the pathogenesis of polyQ diseases. In recent years, however, several examples of mutant transcript toxicity were demonstrated, and additional toxic RNA and protein entities were identified.
Affiliation: Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.