Delivery of oligonucleotide functionalized nanoparticles
The present invention relates to compositions and methods for delivering an oligonucleotide-functionalized nanoparticle.
1. A method of inhibiting gene expression comprising the step of:
administering a therapeutically effective amount of a composition comprising a dermal vehicle and a spherical oligonucleotide-functionalized nanoparticle having a net negative charge to human skin under conditions wherein the oligonucleotide-functionalized nanoparticle hybridizes to a target polynucleotide and inhibits gene expression,
wherein the nanoparticle is from about 5 nanometers (nm) to about 50 nm in mean diameter,
wherein gene expression is inhibited by about 10% or more,
and wherein oligonucleotides are covalently associated with the nanoparticle at a surface density of at least 2 pmol/cm 2 .
2. The method of claim 1 wherein the target polynucleotide is RNA.
3. The method of claim 1 wherein the administration of the composition ameliorates a skin disorder.
4. The method of claim 3 wherein the skin disorder is selected from the group consisting of cancer, a genetic disorder, an aging disorder, inflammation, infection, and cosmetic disfigurement.
5. The method of claim 4 wherein the cancer is selected from the group consisting of squamous cell carcinoma, basal cell carcinoma, breast cancer and melanoma.
6. The method of claim 4 wherein the genetic disorder is selected from the group consisting of epidermolysis bullosa simplex, bullous ichthyosis, pachyonychia congenita, Costello syndrome and tuberous sclerosis.
7. The method of claim 4 wherein the aging disorder is selected from the group consisting of UV-damage and progeria.
8. The method of claim 4 wherein the inflammation is due to psoriasis.
9. The method of claim 8 wherein the target is interleukin-23.
10. The method of claim 4 wherein the infection is selected from the group consisting of viral infection and bacterial infection.
11. The method of claim 4 wherein the cosmetic disfigurement is selected from the group consisting of seborrheic keratoses, epidermal nevi and pigmented nevi.
12. The method of claim 11 wherein the target is a gene product comprising a mutation, said gene product being expressed by a gene selected from the group consisting of FGFR3, K10 and B-Raf.
13. The method of claim 1 wherein gene expression is inhibited by about 20%, about 30%, about 40%, about 50%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, 99%, or more compared to gene expression in the absence of administration of the composition.
14. The method of claim 1 wherein
the nanoparticle is a gold nanoparticle.
15. The method of claim 1 , said dermal vehicle comprising an ointment.
16. The method of claim 15 wherein the ointment is Aquaphor.
17. The method of claim 1 wherein each oligonucleotide is from about 5 to about 100 nucleotides in length.
18. The method of claim 1 wherein each oligonucleotide is from about 5 to about 50 nucleotides in length.
19. The method of claim 1 wherein oligonucleotides are covalently associated with the nanoparticle at a surface density of at least 4 pmol/cm 2 .
20. The method of claim 1 wherein oligonucleotides are covalently associated with the nanoparticle at a surface density of 4 pmol/cm 2 .
21. The method of claim 1 wherein the oligonucleotide comprises a spacer through which the oligonucleotide is covalently bound to the nanoparticle.
22. The method of claim 21 wherein the spacer is a polynucleotide spacer that is at least 10 nucleotides in length.