Mutations in Cu/Zn superoxide dismutase (encoded by SOD1), one of the causes of familial amyotrophic lateral sclerosis (ALS), lead to progressive death of motoneurons through a gain-of-function mechanism. RNA interference (RNAi) mediated by viral vectors allows for long-term reduction in gene expression and represents an attractive therapeutic approach for genetic diseases characterized by acquired toxic properties. We report that in SOD1(G93A) transgenic mice, a model for familial ALS, intraspinal injection of a lentiviral vector that produces RNAi-mediated silencing of SOD1 substantially retards both the onset and the progression rate of the disease.
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Lipid nanoparticles and transcranial focused ultrasound enhance the delivery of SOD1 antisense oligonucleotides to the murine brain for ALS therapy.
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School of Chemistry and Molecular Bioscience, Molecular Horizons, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia. Electronic address:
Article Synopsis
- ALS is a severe neurodegenerative disease characterized by the buildup of misfolded proteins in motor neurons, prompting researchers to find ways to reduce this burden for potential treatment.
- Antisense oligonucleotides (ASOs) have been identified as a promising option to target proteins like SOD1 that cause mutations, but their delivery to the central nervous system is challenging due to the blood-brain barrier.
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