Down Syndrome: a potential treatment XISTs

Down Syndrome (DS) is caused by a triplication of genes on chromosome 21 (HSA21) and gives rise to mental retardation (MR). Silencing of one of three copies of HSA21 has been shown to rescue the cell phenotype. In our prior funded work, we have developed several approaches to overcome the technical hurdles to allow for therapeutic intervention – efficient genomic integration and specific targeting of one of the three HSA21 chromosomes. The current proposal seeks to address whether enhanced efficiency of silencing seen in vitro can be achieved in vivo. After lentiviral based infection of the targeting construct into the TcMAC21 DS mouse model, we will evaluate whether these mice show normalization in phenotype at the behavioral, neurophysiological, histological and genetic/epigenetic levels.