Methods and compositions for improved deliver, expression or activity of RNA interference agents
OwnerJessie L.-S. Au, M. Guillaume Wientjes +2inventors
InventorsJessie L.-S. Au, M. Guillaume Wientjes, Ze Lu, Jie Wang
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Abstract
The present disclosure provides methods and compositions for enhanced delivery of siRNA or miRNA, into the interior of multilayered tissues, and into the cytoplasm or nucleus of cells of a tissue. Such methods and compositions yield tumor-selective and intracellular delivery of RNAi agents and allow for RNAi-mediated activity such as knock-down of the target genes and associated products. The current disclosure further provides methods and compositions for improving the intracellular bioavailability of nucleotide agents.
Claims20
An RNAi Delivery and Expression System (RIDES) composition comprising:
- (a) a liposomal formulation, where the lipid component comprises DOTAP, Cholesterol, DOPE, and DSPE-PEG2000 in a molar ratio of about 50:30:19:1, wherein the charge ratio between RNAi agent and DOTAP is between 1:1 and 1:10, wherein the liposomal formulation further contains one or more enabler agents selected from the group consisting of paclitaxel, docetaxel, vincristine, colchicine, nocodazole, and doxorubicin, plus an RNA interference (RNAi) agent selected from the group consisting of small interfering RNA (siRNA), double-stranded RNA (dsRNA), single-stranded RNA (ssRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA);
- and
- (b) a pharmaceutically acceptable carrier.
A composition comprising:
- (a) a liposomal formulation, where the lipid component comprises DOTAP, Cholesterol, DOPE, and DSPE-PEG2000 in a molar ratio of about 50:30:19:1, an RNAi agent, wherein the charge ratio between RNAi agent and DOTAP is between 1:1 and 1:10;
- and wherein the liposomal formulation further contains one or more enabler agents, selected from the group consisting of paclitaxel, docetaxel, vincristine, colchicine, nocodazole and doxorubicin;
- and
- (b) a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.