Aptamer compositions and methods of use thereof
An aptamer platform capable of efficiently delivering and silencing one, two or more genes in vivo or in vitro is provided. Methods of using the aptamer compositions for selectively targeting cells to down-regulate the expression of multiple genes are also provided.
1. A pharmaceutical composition comprising an effective amount of an aptamer-siRNA chimera comprising:
first and second ends, wherein the first and second ends comprise an aptamer that specifically binds a target protein, wherein the first end has a nucleic acid sequence according to SEQ ID NO:35, and the second end has a nucleic acid sequence according to SEQ ID NO:36; and
an siRNA construct between the first and second ends, wherein the siRNA construct is processed by cellular RNAi machinery to produce at least two different siRNAs that specifically inhibit expression of two or more different genes in a cell expressing the target protein, wherein the siRNA construct has a nucleic acid sequence according to SEQ ID NO:37 and SEQ ID NO:38.
2. A method for reducing tumor burden in a subject in need thereof comprising, administering to the subject an effective amount of the pharmaceutical composition according to claim 1 .
3. The method of claim 2 , wherein the subject has breast cancer.
4. The method of claim 2 , wherein the target protein of the siRNA is EGFR.
5. The method of claim 4 , wherein the two or more different genes bound by the aptamers comprise HER2 and HER3 oncogene expressed by the cancer cell.
6. A method of reducing tumor associated angiogenesis in a subject in need thereof comprising:
administering to the subject an effective amount of the pharmaceutical composition of claim 1 .
7. The method of claim 2 , wherein the subject has breast cancer.