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Can I read Di-valent siRNA-mediated silencing of MSH3 blocks somatic repeat expansion in mouse models of Huntington’s disease on EtoBox?
Di-valent siRNA-mediated silencing of MSH3 blocks somatic repeat expansion in mouse models of Huntington’s disease by Daniel O'Reilly; Jillian Belgrad; Chantal Ferguson; Ashley Summers; Ellen Sapp; Cassandra McHugh; Ella Mathews; Adel Boudi; Julianna Buchwald; Socheata Ly; Dimas Moreno; Raymond Furgal; Eric Luu; Zachary Kennedy; Vignesh Hariharan; Kathryn Monopoli; X. William Yang; Jeffery Carroll; Marian DiFiglia; Neil Aronin; Anastasia Khvorova is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Di-valent siRNA-mediated silencing of MSH3 blocks somatic repeat expansion in mouse models of Huntington’s disease about?
Huntington’s disease (HD) is a severe neurodegenerative disorder caused by the expansion of the CAG trinucleotide repeat tract in the huntingtin gene. Inheritance of expanded CAG repeats is needed for HD manifestation, but further somatic expansion of the repeat tract in non-dividing cells, particularly striatal neurons, hastens disease onset. Called somatic repeat expansion, this process is mediated by the mismatch repair (MMR) pathway. Among MMR components identified as modifiers of HD onset, MutS homolog 3 (MSH3) has emerged as a potentially safe and effective target for therapeutic intervention. Here, we identify a fully chemically modified short interfering RNA (siRNA) that robustly silences Msh3 in vitro and in vivo. When synthesized in a di-valent scaffold, siRNA-mediated silencing of Msh3 effectively blocked CAG-repeat expansion in the striatum of two HD mouse models without affecting tumor-associated microsatellite instability or mRNA expression of other MMR genes. Our findings establish a promising treatment approach for patients with HD and other repeat expansion diseases.
Who reads Di-valent siRNA-mediated silencing of MSH3 blocks somatic repeat expansion in mouse models of Huntington’s disease?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Daniel O'Reilly; Jillian Belgrad; Chantal Ferguson; Ashley Summers; Ellen Sapp; Cassandra McHugh; Ella Mathews; Adel Boudi; Julianna Buchwald; Socheata Ly; Dimas Moreno; Raymond Furgal; Eric Luu; Zachary Kennedy; Vignesh Hariharan; Kathryn Monopoli; X. William Yang; Jeffery Carroll; Marian DiFiglia; Neil Aronin; Anastasia Khvorova
- Publisher
- Elsevier BV
- Published
- 2023
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)