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Project #4

GENE-REGULATORY SPHERICAL NUCLEIC ACIDS (SNAS) FOR GLIOBLASTOMA

Prof. Chad A. Mirkin
Prof. Alexander Stegh

Malignant brain tumors are aggressive and considered one of the deadliest of all human cancers. Treatment options are limited and at best offer temporary relief from progressive tumor growth. Brain tumors are comprised of many cell subpopulations that confer the tumor with an astonishing ability to overcome nearly any radiation and/or chemotherapy treatment. This characteristic is due, in part, to a complex intratumoral landscape of genetic and epigenetic changes. Informed by the tumor’s genetic and epigenetic makeup, several ‘targeted’ pharmacologicals have been approved for the treatment of brain cancers, foremost inhibitors of known cancer-associated enzymatic activities. While initial response rates were observed in a small fraction of brain tumor patients, tumor recurrence is nearly universal.

The overarching goals of this project are the development of gene-regulatory spherical nucleic acids (SNAs) targeted to the glioma oncogene IDH1, combined with small molecule-based IDH1 inhibitors to regulate cellular metabolism of glioma cells. Prior studies from the Stegh laboratory identified IDH1 as a critical glioma oncogene that promotes glioma progression (Calvert et al, 2017, Cell Reports).

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