Chiral design

A method for inhibiting expression or reducing activity of a protein, comprising contacting a nucleic acid polymer encoding the protein with a composition, wherein the composition is a chirally controlled oligonucleotide composition comprising oligonucleotides of a particular oligonucleotide type defined by having:

• 1) a common base sequence and length;
• 2) a common pattern of backbone linkages;
• and
• 3) a common pattern of backbone chiral centers,
• which composition is chirally controlled in that it is enriched, relative to a substantially racemic preparation of oligonucleotides having the same base sequence and length, for oligonucleotides of the particular oligonucleotide type, wherein:
• the common base sequence has at least 17 bases;
• at least 50% of chiral internucleotidic linkages in each oligonucleotide of the particular oligonucleotide type are Sp;
• and
• the common pattern of backbone chiral centers comprises from 5′ to 3′ Rp(Sp)2;
• wherein the common base sequence is complementary to that of a nucleic acid encoding the protein.