Citations 1
Artificial microRNA suppresses C9ORF72 variants and decreases toxic dipeptides in vivo
Cabrera, Gabriela Toro , Meijboom, Katharina E. , Abdallah, Abbas, Foster, Zachariah W. , Weiss, Alexandra , Wightman, Nicholas, Stock, Rachel , Gruntman, Alisha M. , Giampetruzzi, Anthony, Petrucelli, Leonard , Brown, Robert C., Mueller, Christian , Tran, Helen, Weiss, Alexandra, Gendron, Tania F. , Brown, Robert
No container title available | September 23, 2022 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects motor neurons, causing progressive muscle weakness and respiratory failure. The presence of an expanded hexanucleotide repeat in chromosome 9 open reading frame 72 (C9ORF72) accounts for most cases of familial ALS and frontotemporal dementia (FTD). To determine if suppressing expression of C9ORF72 gene products can reduce toxicity, we designed a set of artificial microRNAs (amiRNA) targeting the human C9ORF72 gene. Here we report that an AAV9-mediated amiRNA significantly suppresses expression of the C9ORF72 mRNA, protein, and toxic poly-dipeptides generated by the expanded repeat in the brain and spinal cord.