Chk1-targeting sirnas chemically modified with gemcitabine
AssigneeSirnaomics, Inc.
InventorsBhaskar HALAMI, Vera SIMONENKO, Wookhyun KIM, Daniel MUTISYA, David M. EVANS
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Abstract
Compositions comprising uniquely methyl- and fluoro-modified, Chk1-targeting siRNAs incorporating one or more gemcitabine molecules are provided. Methods of formulating the compositions also are provided, together with methods for using the composition for treating a variety of cancers and other disorders and diseases in mammals.
Claims20
A pharmaceutical composition comprising a modified, interfering ribonucleic acid (RNAi) molecule that inhibits expression of Chk1, comprising gemcitabine moieties in the place of one or more cytidine residues, and further comprising a histidine-lysine copolymer carrier, wherein the RNAi is selected from the group consisting of siRNA, miRNA, and shRNA and mRNA.
A pharmaceutical composition comprising a first siRNA that inhibits expression of Chk1 and a second siRNA that inhibits expression of WEE1,
- wherein the first siRNA comprises sense and antisense strands selected from the group consisting:
- SEQ. ID Nos. 3 and 4;
- SEQ. ID Nos. 5 and 6;
- SEQ. ID Nos. 7 and 8;
- SEQ. ID Nos. 9 and 10;
- and SEQ. ID Nos. 11 and 12,
- wherein said second siRNA comprises a sense strand comprising SEQ. ID Nos 13 or SEQ ID NO:
- 14,
- wherein said siRNAs optionally comprise one or more modifications selected from the group consisting of 2′-OMe, 2′-F and phosphorothioate modifications, and
- wherein said composition further comprises a histidine-lysine copolymer carrier.
A method of treating cancer in a subject comprising administering to the subject a pharmaceutically effective amount of a pharmaceutical composition comprising an siRNA comprising SEQ. ID Nos. 5 and 6 and an siRNA have a sense strand comprising SEQ. ID No. 14, wherein the composition further comprises HKP(+H), and wherein the pharmaceutical composition is administered through intravenous or intratumoral injection.
The method according to claim 16, wherein the subject is a human.
Dependencies are inferred from the claim text.