DNAzyme Cleavage of CAG Repeat RNA in Polyglutamine Diseases

• DOI: 10.1007/s13311-021-01075-w
• Publication Date: 2021-06-23T14:05:40Z
• Authors: Nan Zhang; Brittani Bewick; Jason Schultz; Anjana Tiwari; Robert Krencik; Aijun Zhang; Kaho Adachi; Guangbin Xia; Kyuson Yun; Partha Sarkar; Tetsuo Ashizawa
• Keywords: Deoxyribozyme; Aggresome; RNA Silencing; Cleavage (geology)

CAG repeat expansion is the genetic cause of nine incurable polyglutamine (polyQ) diseases with neurodegenerative features. Silencing RNA holds great therapeutic value. Here, we developed a repeat-based RNA-cleaving DNAzyme that catalyzes destruction expanded six polyQ high potency. preferentially cleaved allele in spinocerebellar ataxia type 1 (SCA1) cells. While cleavage was non-allele-specific for 3 (SCA3) cells, treatment leads to improved cell viability without affecting mitochondrial metabolism or p62-dependent aggresome formation. appears be stable mouse brain at least month, and an intermediate dosage SCA3 model significant reduction molecular weight ATXN3 proteins. Our data suggest effective silencing molecule potential multiple diseases.