Oligonucleotide compositions and methods thereof

A method for treating Duchenne muscular dystrophy, comprising administering to a subject susceptible thereto or suffering therefrom an oligonucleotide composition comprising a first plurality of oligonucleotides of a particular oligonucleotide type defined by:

• 1) base sequence;
• 2) pattern of backbone linkages;
• 3) pattern of backbone chiral centers;
• and
• 4) pattern of backbone phosphorus modifications, which composition is chirally controlled in that it is enriched, relative to a substantially racemic preparation of oligonucleotides having the same base sequence, for oligonucleotides of the particular oligonucleotide type,
• wherein:
• oligonucleotides of particular oligonucleotide type each comprise:
• 1) a 5′-end region comprising 2 or more consecutive nucleoside units each comprising a 2′-F modified sugar moiety;
• 2) a 3′-end region comprising 2 or more consecutive nucleoside units each comprising a 2′-F modified sugar moiety;
• and
• 3) a middle region between the 5′-end region and the 3′-region comprising at least one 2′-OR1 modified sugar moiety and at least one 2′-F modified sugar moiety,
• wherein R1 is optionally substituted C1-6 alkyl;
• and
• oligonucleotides of the particular oligonucleotide type are capable of mediating the skipping of exon 51 of the dystrophin gene.