Publications by authors named "Zaneta Kalinowska-Poska"
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.
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- The human genome generally has two copies of each gene, but they often express at unequal levels, which is important for understanding genetic disorders, particularly dominant diseases with one normal and one mutant allele.
- Polyglutamine diseases, like Spinocerebellar ataxia type 3 and Huntington's disease, are caused by CAG repeat expansions in specific genes, making it tough to study their gene expression due to similar CAG sequences.
- The study employed SNP variants linked to normal or expanded alleles to measure gene expression levels specifically, revealing that differentiation affects mRNA ratios and enabling monitoring of therapeutic strategies in relevant cellular models and a mouse model of Huntington's disease.
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.
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