US 8,895,526 B2 · Identification of RNAI targets and use of RNAI for rational therapy of chemotherapy-resistant leukemia and other cancers

Abstract

Provided is a mosaic mouse model for use in determining the potency of an shRNA in vivo for reducing survival of cancer cells of chemotherapy-resistant leukemia. The syngeneic mouse recipient is transplanted with tet-on competent leukemia cells carrying a bicistronic nucleic acid construct comprising a promoter operably linked to a fusion gene associated with chemotherapy-resistant leukemia, and a sequence encoding a reverse tet-transactivator protein, such that both coding sequences are co-expressed from the promoter. Also provided are methods of treating soft tissue cancers.

Claims7

Dependent claims

A method for treating chemotherapeutic-resistant acute myeloid leukemia in a subject in need thereof, wherein the subject exhibits a known genotype associated with a chemotherapy-resistant leukemia, the method comprising:

administering to the subject an RNAi molecule directed against a gene whose expression is necessary for survival of the chemotherapy-resistant acute myeloid leukemia cell with said known genotype and is dispensable for the growth of non-transformed hematopoietic cells, wherein the gene is AOF2, EED, HDAC3, SMARCA4, SMARCD1, SUZ12 or WHSC111 so as to inhibit survival of acute myeloid leukemia cells in the subject, and thereby treat the chemotherapeutic-resistant acute myeloid leukemia in the subject.

Dependencies are inferred from the claim text.

Facts

Application

13/260,540Filed 29 Mar 2010 · us provisional application

Priority

27 Mar 2009

Published

US 2012/0272346 A125 Oct 2012

Granted

25 Nov 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification20 codes

A61K 31/185
Medicinal preparations containing organic active ingredients: acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic…
A01K 67/0271
New or modified breeds of vertebrates: chimeric vertebrates, e.g. comprising exogenous cells
A61P 35/02
Antineoplastic agents: specific for leukemia
C12N 15/111
DNA or RNA fragments; Modified forms thereof ; Non-coding nucleic acids having a biological activity: general methods applicable to biologically…

Identification of RNAI targets and use of RNAI for rational therapy of chemotherapy-resistant leukemia and other cancers

Life of this patent

Identification of RNAI targets and use of RNAI for rational therapy of chemotherapy-resistant leukemia and other cancers

Life of this patent

Abstract

Claims7