Artificial microRNA suppresses C9ORF72 variants and decreases toxic dipeptide repeat proteins in vivo.
Gene Ther
; 31(3-4): 105-118, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-37752346
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) is the most frequent mutation causing 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 dipeptide repeat proteins generated by the expanded repeat in the brain and spinal cord of C9ORF72 transgenic mice.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Neurodegenerativas
/
MicroRNAs
/
Esclerose Lateral Amiotrófica
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Gene Ther
Assunto da revista:
GENETICA MEDICA
/
TERAPEUTICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos