Targeted inhibition using engineered oligonucleotides

An antisense oligonucleotide or salt thereof comprising a polynucleotide sequence, wherein the antisense oligonucleotide or salt thereof is at least partially complementary to at least a portion of at least a first and a second RNA originating from two genetic loci that are associated with a disease or condition, wherein at least a portion of the first or the second RNA is encoded in a IRX5 gene, wherein when the antisense oligonucleotide or salt thereof at least partially binds to the first RNA, a first region of at least seven contiguous bases in the antisense oligonucleotide are complementary to contiguous nucleic acids contained within the first RNA, and a second region of at least five contiguous bases in the antisense oligonucleotide are complementary to contiguous nucleic acids contained within the first RNA, and wherein when the antisense oligonucleotide or salt thereof at least partially binds to the second RNA, a first region of at least seven contiguous bases in the antisense oligonucleotide are complementary to contiguous nucleotides contained within the second RNA, and a second region of at least five contiguous bases in the antisense oligonucleotide are complementary to contiguous nucleotides contained within the second RNA, and wherein a predicted Gibbs free energy (ΔG) of binding of the antisense oligonucleotide to the first and the second RNA ranges, individually, from about −17 to about −36 kcal mol−1 at about 37 degrees Celsius and at a pH ranging from about 7.2 to about 7.6, wherein the antisense oligonucleotide or salt thereof comprises at least one chemically modified nucleotide.