Oligonucleotide compositions and methods thereof

A method for characterizing a chirally controlled oligonucleotide composition, the method comprising:

• assessing complement activation by the chirally controlled oligonucleotide composition relative to a reference oligonucleotide composition;
• wherein:
• the chirally controlled oligonucleotide composition comprises a plurality of oligonucleotides of a particular oligonucleotide type which are structurally identical;
• which composition is chirally controlled in that it is enriched, relative to a substantially racemic preparation of oligonucleotides of the particularly oligonucleotide type, for oligonucleotides of the particular oligonucleotide type;
• oligonucleotides of the plurality comprises 5 or more phosphorothioate internucleotidic linkages, wherein at least about 50% phosphorothioate internucleotidic linkages are Sp;
• the reference oligonucleotide composition is a substantially racemic preparation of oligonucleotides of the particularly type;
• and
• wherein the reference oligonucleotide composition increases complement activation compared to absence of the reference oligonucleotide composition.