Targeted inhibition using engineered oligonucleotides

An engineered oligonucleotide or salt thereof comprising a polynucleotide sequence from 15-30 nucleotides in length, wherein the engineered oligonucleotide or salt thereof:

• a) is at least partially complementary to at least a portion of at least a first and a second mRNA originating from two genetic loci that are associated with a disease or condition;
• b) is non-naturally encoded miR-30 miRNA;
• c) comprises at least 90% sequence identity to a sequence selected from SEQ ID NO:
• 38, SEQ ID NO:
• 39, SEQ ID NO:
• 40, SEQ ID NO:
• 41, SEQ ID NO:
• 42, SEQ ID NO:
• 43, SEQ ID NO:
• 44, SEQ ID NO:
• 45, SEQ ID NO:
• 624, SEQ ID NO:
• 625, SEQ ID NO:
• 626, SEQ ID NO:
• 627, SEQ ID NO:
• 629, SEQ ID NO:
• 630, SEQ ID NO:
• 632, SEQ ID NO:
• 633, SEQ ID NO:
• 635, SEQ ID NO:
• 636, SEQ ID NO:
• 637, SEQ ID NO:
• 638, SEQ ID NO:
• 639, SEQ ID NO:
• 640, SEQ ID NO:
• 641, SEQ ID NO:
• 642, and SEQ ID NO:
• 643, as determined by a BLAST pairwise sequence alignment algorithm;
• d) comprises one or more nucleotide insertions, nucleotide deletions, nucleotide substitutions, or any combination thereof, relative to one or more otherwise comparable naturally encoded, mature miR-30 miRNA;
• and,
• e) comprises about 10% lower Gibbs free energy (AG) of binding or lower, relative to a ΔG of binding of the otherwise comparable mature miR-30 miRNA binding to both the first and the second mRNA, wherein the bindings are at about 37 degrees Celsius and at a pH ranging from about 7.2 to about 7.6.