CRISPR/Cas9-based silencing of the ATXN1 gene in Spinocerebellar ataxia type 1 (SCA1) fibroblasts
Salvatori, F.; Pappadà, M.; Sicurella, M.; Buratto, M.; Simioni, V.; Tugnoli, V.; Marconi, P.
Show abstract
Spinocerebellar Ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by a gain-of-function protein with toxic activities, containing an expanded polyQ tract in the coding region. Actually, there are no treatments available to delay the onset, stop or slow down the progression of this pathology. Many approaches developed over the years involve the use of siRNAs and antisense oligonucleotides (ASOs). Here we develop and validate a CRISPR/Cas9 therapeutic strategy in fibroblasts isolated from SCA1 patients. We started from the screening of 10 different sgRNAs able to recognize regions upstream and downstream the CAG repeats, in exon 8 of ATXN1 gene. The two most promising sgRNAs, G3 and G8, whose efficiency was evaluated with an in vitro system, significantly downregulated the ATXN 1 protein expression. This downregulation was due to the introduction of indels mutations into the ATXN1 gene. Notably, with an RNA-seq analysis, we demonstrated minimal off-target effects of our sgRNAs. These preliminary results support CRISPR/Cas9 as a promising approach for treated polyQ-expanded diseases.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Functional characterization of Neurofilament Light b splicing and misbalance in zebrafish 93%
- Tissue-specific vulnerability to apoptosis in Machado-Joseph disease 92%
- Heterologous HSPC transplantation rescues neuroinflammation and ameliorates peripheral manifestations in the mouse model of lysosomal transmembrane enzyme deficiency, MPS IIIC. 91%
Similar papers in this journal
- Identification of ATP2B4 regulatory element containing functional genetic variants associated with severe malaria 93%
- Transcriptional and Histone acetylation changes associated with CRE elements expose key factors governing the regulatory circuit in early stage of Huntington's disease models. 92%
- Defining Mechanistic Links Between the Non-Coding Variant rs17673553 in CLEC16A and Lupus Susceptibility 92%
Similar papers in this journal
Similar papers in this journal
- APOBEC3B reporter myeloma cell lines identify DNA damage response pathways leading to APOBEC3B expression 94%
- Characterization of Poldip2 knockout mice: avoiding incorrect gene targeting 92%
- Anti-cancer compound screening identifies Aurora Kinase A inhibition as a means to favor CRISPR/Cas9 gene correction over knock-out 92%
Similar papers in this journal
- Targeted attenuation of elevated histone marks at SNCA alleviates α-synuclein in Parkinson's disease 93%
- Proteasome subunit PSMC3 variants cause neurosensory syndrome combining deafness and cataract due to proteotoxic stress 91%
- LAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.