AAV-Mediated CAG-Targeting Selectively Reduces Polyglutamine-Expanded Protein and Attenuates Disease Phenotypes in a Spinocerebellar Ataxia Mouse Model.

Polyglutamine (polyQ)-encoding CAG repeat expansions represent a common disease-causing mutation responsible for several dominant spinocerebellar ataxias (SCAs). PolyQ-expanded SCA proteins are toxic for cerebellar neurons, with Purkinje cells (PCs) being the most vulnerable. RNA interference (RNAi) reagents targeting transcripts with expanded CAG reduce the level of various mutant SCA proteins in an allele-selective manner in vitro and represent promising universal tools for treating multiple CAG/polyQ SCAs.

Selective transduction of cerebellar Purkinje and granule neurons using delivery of AAV-PHP.eB and AAVrh10 vectors at axonal terminal locations.

Adeno-associated virus (AAV)-based brain gene therapies require precision without off-targeting of unaffected neurons to avoid side effects. The cerebellum and its cell populations, including granule and Purkinje cells, are vulnerable to neurodegeneration; hence, conditions to deliver the therapy to specific cell populations selectively remain challenging. We have investigated a system consisting of the AAV serotypes, targeted injections, and transduction modes (direct or retrograde) for targeted delivery of AAV to cerebellar cell populations.

Retrograde capabilities of adeno-associated virus vectors in the central nervous system.

Adeno-associated virus (AAV) vectors delivered at the axonal terminals can be retrogradely transported toward neuronal cell bodies throughout the axons. This retrograde phenomenon can serve as a powerful tool for experiments and gene therapy using AAVs. The advantages of using AAV vectors delivered retrogradely are greater cellular specificity, high transduction efficiency, increased safety, and absence of cytotoxicity.

Characterisation of genome-wide structural aberrations in canine mammary tumours using single nucleotide polymorphism (SNP) genotyping assay.

Characterisation of copy number variation (CNV) and loss of heterozygosity (LOH) has pro- vided evidence for the relationship of this type of genetic variation with the occurrence of a broad spectrum of diseases, including cancer lesions. The role of CNVs and germinal or somatic LOHs in canine mammary tumours is still unknown. Therefore, the aim of this study was to identify CNVs and LOHs in canine mammary tumours.