Hybrid oligonucleotides and uses thereof

A composition comprising:

• (i) a first single stranded oligonucleotide having the general formula:
• (Xm1-Xn2-Xo3),
• wherein each instance of X1, X3 is independently a modified nucleotide or unmodified ribonucleotide, wherein m and o are independently integers in a range of 1 to 10, reflecting the number of instances of X1 and X3, respectively, linked consecutively together through internucleotide linkages, wherein each instance of X2 is a deoxyribonucleotide, wherein n is an integer in a range of 6 to 20, reflecting the number of instances of X2 linked consecutively together through internucleotide linkages;
• and
• (ii) a second single stranded oligonucleotide of 4 to 40 nucleotides in length having the general formula:
• (Xp4-Xq5)r,
• wherein each instance of X4 is a modified nucleotide or unmodified ribonucleotide, wherein each instance of X5 is a deoxyribonucleotide, wherein p and q are independently 0 or 1, reflecting the number of instances of X4 and X5, respectively, wherein at least one of X4 and X5 is present and at least one of p and q is 1 in each instance of the unit, (Xp4-Xq5), wherein r is an integer from 2 to 20 reflecting the number of instances of the unit, (Xp4-Xq5), linked together through internucleotide linkages, wherein the second single stranded oligonucleotide does not contain a sequence of more than 5 consecutive deoxyribonucleotides, and wherein the symbol “-” denotes an internucleotide linkage,
• wherein the first single stranded oligonucleotide is linked to the second single stranded oligonucleotide through an internucleotide linkage in the following orientation:
• 5′(Xm1-Xn2-Xo3)-(Xp4-Xq5)r3′;
• wherein the first single stranded oligonucleotide comprises a cleavage promoting region and the second single stranded oligonucleotide comprises a protecting region, wherein the cleavage promoting region is a gapmer and the protecting region is a mixmer, and
• wherein the first single stranded oligonucleotide and the second single stranded oligonucleotide are complementary to a target mRNA and selectively cleave the target mRNA, wherein the first single stranded oligonucleotide and the second single stranded oligonucleotide are complementary to adjacent sites of the target mRNA, wherein the first oligonucleotide comprises a region of complementarity that is complementary with a portion of the 3′ UTR of the target mRNA;
• and wherein the portion of the 3′ UTR of the target mRNA is 5′ to one or more miRNA binding elements or a repeat region of the target mRNA.