hASO1

hASO1 (also known as BIIB101 or ION859) is an antisense oligonucleotide (ASO) designed to suppress the expression of the human *SNCA* gene, which encodes the alpha-synuclein (aSyn) protein. It is a 20-mer gapmer consisting of a 10-base phosphorothioate (PS)-modified DNA core flanked by 5-base 2'-methoxyethyl (MOE)-modified RNA wings. This structure facilitates the recruitment of RNase H1 to degrade the target *SNCA* mRNA, thereby reducing the production of aSyn protein. Developed by Ionis Pharmaceuticals and Biogen, hASO1 was investigated as a disease-modifying therapy for Parkinson's disease and other synucleinopathies to prevent or reverse the accumulation of toxic aSyn aggregates. While it showed robust reduction of aSyn in the brain and CSF of non-human primates, the clinical candidate BIIB101 was eventually discontinued from Biogen's pipeline in early 2023.

Other names

SNCA ASOalpha-synuclein antisense oligonucleotide