Allele-Specific Gene Silencing

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Allele-Specific Gene Silencing

Cardiac arrhythmias are a major healthcare problem in the developed world. The American Heart Association 2017 statistical report indicates that atrial fibrillation, the most common cardiac rhythm disorder, has an ≈25% lifetime incidence and annual costs of ≈26 billion dollars, whereas sudden cardiac death (usually caused by malignant arrhythmias) affects fewer individuals (just under 200 000 A...

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Allele-specific silencing of dominant disease genes.

Small interfering RNA (siRNA) holds therapeutic promise for silencing dominantly acting disease genes, particularly if mutant alleles can be targeted selectively. In mammalian cell models we demonstrate that allele-specific silencing of disease genes with siRNA can be achieved by targeting either a linked single-nucleotide polymorphism (SNP) or the disease mutation directly. For a polyglutamine...

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Allele-specific gene expression uncovered.

Genetic variation in populations can result in variation in levels of gene expression but the extent to which this occurs has been unclear. In this article, recent studies of allele-specific expression among autosomal non-imprinted genes are reviewed. These new data provide evidence that differential expression is relatively common and that allelic differences are heritable and can be highly co...

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Enhancement of Allele Discrimination by Introduction of Nucleotide Mismatches into siRNA in Allele-Specific Gene Silencing by RNAi

Allele-specific gene silencing by RNA interference (RNAi) is therapeutically useful for specifically inhibiting the expression of disease-associated alleles without suppressing the expression of corresponding wild-type alleles. To realize such allele-specific RNAi (ASP-RNAi), the design and assessment of small interfering RNA (siRNA) duplexes conferring ASP-RNAi is vital; however, it is also di...

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Assessment of allele-specific gene silencing by RNA interference with mutant and wild-type reporter alleles

Allele-specific gene silencing by RNA interference (RNAi) is therapeutically useful for specifically suppressing the expression of alleles associated with disease. To realize such allele-specific RNAi (ASPRNAi), the design and assessment of small interfering RNA (siRNA) duplexes conferring ASP-RNAi is vital, but is also difficult. Here, we show ASP-RNAi against the Swedish- and London-type amyl...

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ژورنال

عنوان ژورنال: Circulation Research

سال: 2017

ISSN: 0009-7330,1524-4571

DOI: 10.1161/circresaha.117.311541