Compositions and methods of using transposons

Abstract

The present invention provides compositions and methods of using transposons. In one aspect, methods are disclosed that are useful for identifying negatively selected genes in an insertional mutagenesis screen. In another aspect, compositions for reducing proliferation of a tumor cell expressing an oncogenic RAS include an activator of a WNT pathway. Pharmaceutical compositions for reducing proliferation of tumor cells in a subject in need thereof by administering an effective amount of an activator of a WNT pathway to the tumor cells of the subject are also disclosed.

Description

[0001] Cross References to Related Applications [0002] This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 61 / 905,819, filed November 18, 2013, which is hereby incorporated by reference in its entirety. Background of the invention [0003] Recent advances in sequencing technology have enabled the identification of specific mutations in individual tumors, raising the possibility of developing targeted therapies for specific tumors. Functional genomics has proven to be a powerful approach for uncovering the underlying drivers of human biological and disease processes. CRISPR-Cas9 and shRNA libraries provide efficient screening tools to knock out or knock down protein-coding genes. Targeting specific oncogenic alterations and pathways in tumor cells has been found to be highly effective in treating some cancers, including HER2-amplified breast cancer and acute promyelocytic leukemia. However, for many common mutations including ...

AI Technical Summary

Problems solved by technology

While loss-of-function screens of cancer cells using shRNA libraries have been successfully employed to identify synthetic lethal targets, genome-wide gain-of-function screens for negatively selected genes are lacking

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