The Ly Group

Bioorganic Chemistry  •  Combinatorial Chemistry  •  Chemical Genetics  •  Functional Genomics


Unstable Repeat Disorders

example found in nature

To date more than 20 genetic diseases have been associated with unstable repeat expansion, including fragile X syndrome, dystrophia myotonica 1 and 2, Huntingtin disease and Machado-Joseph disease, just to name a few. These unstable repeats cause either loss or altered protein functions, or in some cases altered RNA functions; and presently there are no effective treatments for such genetic diseases. Our effort in this area is focused on the development of Janus-based ╬│-peptide nucleic acids (J-╬│PNAs) for targeting unstable repeated regions within genomic DNA and RNA. Our current emphasis is on MD1, a type of muscular dystrophy and mental retardation caused by gain of RNA function. The goal is to develop a relatively short nucleic acid reagent (preferentially 3nt in length) that can invade the CUG repeat and thereby prevents the MBNL1 splicing factor from binding to it. In doing so will free MBNL1, allowing it to execute its function in the cytoplasm and thereby reverting the phenotype.