SCREENING METHOD FOR SELECTED AMINO LIPID-CONTAINING COMPOSITIONS
The invention features a method of identifying therapeutically relevant compositions which include a therapeutic agent and 2,2-Dilinoley 1-4-dimethylaminomethyl-[1,3]-dioxolane by screening for an effect of the agent on the liver of a model subject.
1 . A method of evaluating a composition that includes a therapeutic agent and 2,2-Dilinoley 1-4-dimethylaminomethyl-[1,3]-dioxolane comprising:
providing a composition that includes a therapeutic agent and 2,2-Dilinoley 1-4-dimethylaminomethyl-[1,3]-dioxolane;
administering the composition to a test animal; and
determining the effect of the composition on the expression of a target gene expressed in the liver of the animal,
thereby evaluating the composition.
2 . The method of claim 1 , wherein the therapeutic agent is an RNA-based construct.
3 . The method of claim 2 , wherein the RNA-based construct is a dsRNA.
4 . The method of claim 1 , wherein the target gene is Factor VII.
5 . The method of claim 1 , wherein determining the effect of the composition comprises determining target protein levels.
6 . The method of claim 1 , wherein determining the effect of the composition comprises determining target mRNA levels.
7 . The method of claim 5 , wherein the level of target protein in blood is determined.
8 . The method of claim 6 , wherein the level of target mRNA in liver is determined.
9 . The method of claim 1 , further comprising comparing expression of the target gene with a preselected reference value.
10 . The method of claim 1 , wherein the composition further comprises a third component.
11 . The method of claim 1 , wherein the therapeutic agent is an antisense RNA, ribozyme or microRNA.
12 . The method of claim 1 , wherein the test animal is a rodent.
13 . The method of claim 1 , wherein the test animal is a mouse.
14 . The method of claim 1 , wherein the composition reduces FVII protein or mRNA levels in the blood.
15 . The method of claim 1 , wherein the composition reduces FVII protein or mRNA levels in the liver.
16 . The method of claim 1 , wherein the composition further comprises a PEG-modified lipid.
17 . The method of claim 1 , wherein the PEG of the PEG-modified lipid has a size of about 2000 daltons.
18 . The method of claim 16 , wherein the PEG-modified lipid is PEG-DMG, PEG-C-DOMG or PEG-DMA.
19 . The method of claim 18 , wherein the PEG-modified lipid is PEG-DMG.