Bioactive conjugates for oligonucleotide delivery

A method for selectively delivering a compound to the kidneys of a patient, comprising administering the compound to the patient intravenously, wherein the compound has a structure of Formula I:

• wherein:
• O is a double-stranded nucleic acid comprising a first oligonucleotide and a second oligonucleotide, wherein:
• (1) the first oligonucleotide comprises at least 16 contiguous nucleotides, a 5′ end, a 3′ end, and complementarity to a target;
• (2) the second oligonucleotide comprises at least 15 contiguous nucleotides, a 5′ end, a 3′ end, and homology with a target;
• and
• (3) a portion of the first oligonucleotide is complementary to a portion of the second oligonucleotide;
• L is a divalent or trivalent linker:
• Xc is a hydrophobic moiety;
• and
• Zc is a phosphodiester or phosphodiester derivative, or is absent, and wherein Xc is a polyunsaturated moiety having three or more double bonds.

A method for treating a disease or disorder of the kidneys in a patient in need of such treatment, comprising administering to the patient a compound having a structure of Formula I:

• wherein:
• O is a double-stranded nucleic acid comprising a first oligonucleotide and a second oligonucleotide, wherein:
• (1) the first oligonucleotide comprises at least 16 contiguous nucleotides, a 5′ end, a 3′ end, and complementarity to a target:
• (2) the second oligonucleotide comprises at least 15 contiguous nucleotides, a 5′ end, a 3′ end, and homology with a target:
• and
• (3) a portion of the first oligonucleotide is complementary to a portion of the second oligonucleotide:
• L is a divalent or trivalent linker:
• Xc is a hydrophobic moiety:
• and
• Zc is a phosphodiester or phosphodiester derivative, or is absent.