Regulation of oncogenes by microRNAs
AssigneeYale University
InventorsFrank J. Slack, Steven M. Johnson, Helge Grosshans, Joanne Barnes Weidhaas
Life of this patent
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Abstract
Naturally occurring miRNAs that regulate human oncogenes and methods of use thereof are described. Suitable nucleic acids for use in the methods and compositions described herein include, but are not limited to, pri-miRNA, pre-miRNA, mature miRNA ,or fragments of variants thereof that retain the biological activity of the mature miRNA and DNA encoding a pri-miRNA, pre-miRNA, mature miRNA, fragments or variants thereof, or regulatory elements of the miRNA. The compositions are administered to a subject prior to administration of a cytotoxic therapy in an amount effective to sensitize cells or tissues to be treated to the effects of the cytotoxic therapy.
Claims11
A method for increasing the sensitivity of a cell to radiotherapy comprising:
- administering a composition comprising a let-7 miRNA and a suitable pharmaceutical carrier to a cell of a patient, that binds to and inhibits the expression of an mRNA encoded by an oncogene containing a let-7 complementary site (LCS) selected from the group consisting of NRAS, KRAS, HRAS, MYC, MYCL1, MYCN, BCL2, BCL2L1, BCL2L2, TERT, VEGF, EGF, EGFR, ERBB3, GRB2, RAF1, ARAF, MAP2K2, MAPK1, MAPK3, MET, KIT, TP73L(AIX), CCND1, CDK4, MDM2, FES, FURIN, INSL3, CSFIR, MYBL2, MYB, PIK3CD, PIK3C2B, PIK3CG, PIK3R5, AKT1, HLIN-41, VDR, PXR, FOXA1, FOXA2, ASH1L, ARID1B, GR, GLI2, 14-3-3zeta, MO25, SMGI, FRAP1, PER2 and AKT3 in a cell of a patient, and
- subsequently administering radiation to said patient,
- wherein said let-7 miRNA is administered in an effective amount to sensitize the cell to said radiotherapy and wherein said let-7 miRNA is selected from the group consisting of let-7a1, let-7a2, let-7a3, let-7b, let-7c, let-7d, let-7f, let-7h, let-7i, and mir-98.
Dependencies are inferred from the claim text.