System and method for reversible photo-controlled gene silencing

1. A chemically-modified siRNA wherein one or more nucleotides of a strand of the siRNA are replaced with a spacer comprising an azobenzene or a derivative thereof.

2. The siRNA of claim 1 , wherein the one or more nucleotides the spacer replaces are located in the sense strand of the siRNA.

3. The siRNA of claim 1 , wherein two nucleotides of the strand are replaced by the spacer comprising the azobenzene or derivative thereof.

4. The siRNA of claim 1 , wherein the spacer comprising the azobenzene or the derivative thereof is a compound of Formula I:

wherein

L 1 and L 2 are each independently a linker moiety; and

one or more available hydrogen atoms on the phenyl rings is optionally replaced with another group, and

optionally, wherein L 1 and L 2 are each independently C 1-6 alkylene, optionally wherein L 1 and L 2 are each methylene or ethylene.

5. The siRNA of claim 1 , wherein the azobenzene or derivative thereof undergoes isomerization from the trans-configuration to the cis-configuration in the presence of UV light and/or undergoes isomerization from the cis-configuration to the trans-configuration in the presence of visible light.

6. The siRNA of claim 5 , wherein the isomerization from the trans-configuration to the cis-configuration is reversible in the presence of visible light and/or the isomerization from the cis-configuration to the trans-configuration is reversible in the presence of UV light.

7. The siRNA of claim 4 , wherein the one or more available hydrogen atoms in the ortho position on the phenyl rings is replaced with a halogen, optionally chlorine.

8. The siRNA of claim 7 , wherein:

(a) the azobenzene or derivative thereof undergoes isomerization from the trans-configuration to the cis-configuration in the presence of green and/or red light, and/or

(b) the azobenzene or derivative thereof undergoes isomerization from the cis-configuration to the trans-configuration in the presence of blue and/or violet light.

9. The siRNA of claim 1 , wherein the siRNA has higher RNA silencing activity when the azobenzene or derivative thereof is in the trans-configuration compared to the cis-configuration.

10. The siRNA of claim 1 , wherein the siRNA is directed to an oncogene.

11. A method of activating and/or inactivating an siRNA molecule comprising:

(a) providing a chemically-modified siRNA wherein one or more nucleotides of a strand of the siRNA are replaced with a spacer comprising an azobenzene or a derivative thereof, and

(b) exposing the chemically-modified siRNA to light from a light source,

wherein the azobenzene or derivative thereof undergoes isomerization between the cis-configuration and the trans-configuration upon exposure to the light and wherein the chemically-modified siRNA has higher RNA silencing activity when the azobenzene or derivative thereof is in the trans-configuration compared to the cis-configuration.

12. The method of claim 11 , wherein:

(a) the light is UV light and the azobenzene or derivative thereof undergoes isomerization from the trans-configuration to the cis-configuration upon exposure to the UV light,

(b) the light is visible light and the azobenzene or derivative thereof undergoes isomerization from the cis-configuration to the trans-configuration upon exposure to the visible light,

(c) the light is green and/or red light and the azobenzene or derivative thereof undergoes isomerization from the trans-configuration to the cis-configuration upon exposure to the green and/or red light, and/or

(d) the light is blue and/or violet light and the azobenzene or derivative thereof undergoes isomerization from the cis-configuration to the trans-configuration upon exposure to the blue and/or violet light.

13. The method of claim 11 , further comprising introducing the chemically-modified siRNA to a cell, optionally a bacterial cell, a fungal cell, a plant cell or a mammalian cell.

14. The method of claim 13 , wherein the chemically-modified siRNA is exposed to the light source prior or after to introducing the siRNA to the cell.

15. The method of claim 11 , further comprising:

(a) treating a disease associated with increased or aberrant expression of a gene, comprising administering the chemically-modified siRNA to a mammal or cell in need thereof, wherein the chemically-modified siRNA is directed to the gene, or

(b) treating cancer, comprising administering the chemically-modified siRNA to a mammal or cell in need thereof, wherein the siRNA is directed to an oncogene.

16. A method of reversibly silencing gene expression comprising:

(a) providing a cell with a chemically-modified siRNA directed to a gene in the cell, wherein one or more nucleotides of a strand of the siRNA are replaced with a spacer comprising an azobenzene or a derivative thereof, and

(b) exposing the cell to light from a light source that modulates the cis-trans isomerism of the azobenzene or derivative thereof.

17. The method of claim 16 , wherein expression of the gene is decreased when the azobenzene or derivative thereof is in the trans-configuration.

18. The method of claim 17 , wherein expression of the gene is lower when the azobenzene or derivative thereof is in the trans-configuration compared to the cis-configuration.

19. The method of claim 16 , wherein the azobenzene or derivative thereof undergoes isomerization from the cis-configuration to the trans-configuration upon exposure to visible light or upon exposure to green and/or red light.

20. The method of claim 16 , wherein the azobenzene or derivative thereof undergoes isomerization from the trans-configuration to the cis-configuration upon exposure to UV light or under exposure to blue and/or violet light.