Allele-Specific Knockdown of Mutant Huntingtin Protein via Editing at Coding Region Single Nucleotide Polymorphism Heterozygosities.

Huntington's disease (HD) is a devastating, autosomal dominant neurodegenerative disease caused by a trinucleotide repeat expansion in the huntingtin (HTT) gene. Inactivation of the mutant allele by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 based gene editing offers a possible therapeutic approach for this disease, but permanent disruption of normal HTT function might compromise adult neuronal function. Here, we use a novel HD mouse model to examine allele-specific editing of mutant HTT (mHTT), with a BAC97 transgene expressing mHTT and a YAC18 transgene expressing normal HTT.

Polyester nasal swabs collected in a dry tube are a robust and inexpensive, minimal self-collection kit for SARS-CoV-2 testing.

Background: In order to identify an inexpensive yet highly stable SARS-CoV-2 collection device as an alternative to foam swabs stored in transport media, both contrived ("surrogate") CoV-positive and patient-collected spun polyester swabs stored in dry tubes were evaluated for time- and temperature-stability using qPCR.

Methods: Surrogate specimens were prepared by combining multiple, residual SARS-CoV-2-positive clinical specimens and diluting to near-LOD levels in either porcine or human mucus ("matrix"), inoculating foam or polyester nasal swabs, and sealing in dry tubes. Swabs were then subjected to one of three temperature excursions: (1) 4°C for up to 72 hours; (2) 40°C for 12 hours, followed by 32°C for up to 60 hours; or (3) multiple freeze-thaw cycles (-20°C).

Artificial miRNAs Reduce Human Mutant Huntingtin Throughout the Striatum in a Transgenic Sheep Model of Huntington's Disease.

Huntington's disease (HD) is a fatal neurodegenerative disease caused by a genetic expansion of the CAG repeat region in the huntingtin (HTT) gene. Studies in HD mouse models have shown that artificial miRNAs can reduce mutant HTT, but evidence for their effectiveness and safety in larger animals is lacking. HD transgenic sheep express the full-length human HTT with 73 CAG repeats.

Safe and Efficient Silencing with a Pol II, but Not a Pol lII, Promoter Expressing an Artificial miRNA Targeting Human Huntingtin.

Huntington's disease is a devastating, incurable neurodegenerative disease affecting up to 12 per 100,000 patients worldwide. The disease is caused by a mutation in the Huntingtin (Htt) gene. There is interest in reducing mutant Huntingtin by targeting it at the mRNA level, but the maximum tolerable dose and long-term effects of such a treatment are unknown.