Reduced size self-delivering RNAI compounds

1. A composition comprising:

a hydrophobic modified polynucleotide, wherein the polynucleotide is a double stranded RNA, attached to a hydrophobic molecule, wherein the double stranded RNA comprises a guide strand and a passenger strand, wherein the guide strand is from 16-29 nucleotides long and is substantially complementary to a target gene, wherein the passenger strand is from 8-14 nucleotides long and has complementarity to the guide strand, wherein position 1 of the guide strand is 5′ phosphorylated or has a 2′ O-methyl modification, wherein at least 40% of the nucleotides of the double stranded RNA are modified, and wherein the double stranded RNA has one end that is blunt;

a neutral fatty mixture; and

a cargo molecule,

wherein the hydrophobic modified polynucleotide and the neutral fatty mixture forms a micelle.

2. The composition of claim 1 , wherein the 3′ end of the passenger strand is linked to the hydrophobic molecule.

3. The composition of claim 1 , wherein the composition is sterile.

4. The composition of claim 1 , wherein the neutral fatty mixture comprises a DOPC (dioleoylphosphatidylcholine), or a DSPC (distearoylphosphatidylcholine).

5. The composition of claim 1 , wherein the neutral fatty mixture further comprises a sterol, optionally wherein the sterol is cholesterol.

6. The composition of claim 1 , wherein the composition includes at least 20% DOPC and at least 20% cholesterol.

7. The composition of claim 1 , wherein the hydrophobic portion of the hydrophobic modified polynucleotide is a sterol.

8. The composition of claim 1 , wherein the hydrophobic portion of the hydrophobic modified polynucleotide is selected from the group consisting of bile acids, glycolipids, phospholipids, sphingolipids, isoprenoids, vitamins, saturated fatty acids, unsaturated fatty acids, fatty acid esters, triglycerides, pyrenes, porphyrines, adamantane, acridines, coumarin, fluorescein, rhodamine, Texas-Red, digoxygenin, dimethoxytrityl, t-butyldimethylsilyl, t-butyldiphenylsilyl, cyanine dyes, Hoechst 33258 dye, psoralen, and ibuprofen.

9. The composition of claim 1 , wherein the hydrophobic portion of the hydrophobic modified polynucleotide is a polycationic molecule, optionally wherein the polycationic molecule is selected from the group consisting of protamine, arginine rich peptides, and spermine.

10. The composition of claim 1 , wherein the cargo molecule is a lipid, a peptide, vitamin, a small molecule, or a commercially available fat emulsion.

11. The composition of claim 10 , wherein the commercially available fat emulsion is an intralipid or a nutralipid.

12. The composition of claim 1 , wherein the cargo molecule is a fatty acid mixture containing: more than 74% of linoleic acid; at least 6% of cardiolipin; or at least 74% of linoleic acid and at least 6% of cardiolipin.

13. The composition of claim 1 , wherein the cargo molecule is a fusogenic lipid and preferably is at least 10% fusogenic lipid.

14. A method of inducing RNAi in a subject comprising:

administering to a subject an effective amount for inducing RNAi of mRNA of a target gene, a composition of claim 1 , wherein the polynucleotide has at least a region of sequence correspondence to the target gene, and wherein the step of administering is systemic, intravenous, intraperitoneal, intradermal, topical, intranasal, inhalation, oral, intramucosal, local injection, subcutaneous, oral tracheal, or intraocular.

15. The method of claim 14 , wherein the subject is a human.

16. The composition of claim 8 , wherein the bile acid is cholic acid, taurocholic acid, deoxycholate, oleyl litocholic acid or oleoyl cholenic acid.

17. The composition of claim 8 , wherein the porphyrine is Texaphyrine.

18. The composition of claim 8 , wherein the vitamin is biotin.

19. The composition of claim 8 , wherein the cyanine dye is Cy3 or Cy5.