Targeting enhancer RNAs (eRNA) for the treatment of primary brain tumors

­Novel Therapeutic Approach for Glioblastoma

 
Overview
Enhancer RNAs (eRNAs) are transcribed from active enhancer regions of the genome and function to increase the expression of target genes. The expression of specific eRNAs in glioma stem cells is correlated with decreased survival of patients with glioblastomas. Our novel technology uses synthetic oligonucleotides to target and knock out the expression of these eRNAs.
 
Market Opportunity
Current treatment for glioblastomas includes surgical resection of the tumor mass followed by radiation and administration of temozolomide. Yet even with this multi-therapeutic approach, average tumor recurrence time is seven months, and tumor recurrence is almost inevitable. Our technology could lead to the first therapy for glioblastoma that specifically targets glioma stem cells.
 
Innovation and Meaningful Advantages
Enhancer RNAs (eRNAs) are essential for glioma stem cell maintenance, and the expression of certain eRNAs specific to glioma stem cells (GSC) is correlated with decreased survival of patients with glioblastomas. Developing eRNA-targeted therapies could deplete the GSC population and change the course of this deadly disease. Our novel technology uses synthetic oligonucleotides, designed to be resistant to degradation, to target and knock out the expression of specific eRNAs. An alternative technique uses a viral vector encoding an shRNA to target and inhibit expression of the eRNAs. 

Commercial Development: Current State and Next Steps
Our novel technology, which uses synthetic oligonucleotides to target and knock-out the expression of glioblastoma associated eRNAs, works for in vivo applications. An alternative technique uses a viral vector, a lentivirus, to deliver an shRNA (a type of synthetic RNA molecule) that targets and inhibits expression of eRNAs. The synthesized oligonucleotides and viruses are highly specific for the targeted eRNA and have no effect on other genes. 

Collaboration Opportunity
Our goal is to collaborate with biopharma partners who can bring into play the developmental, translational, and financial resources needed to advance this technology through regulatory approval and into the commercial marketplace.

Principal Investigator
Nikos Tapinos,MD, PhD
Associate Professor of Neurosurgery
Brown University
Brown Tech ID #3072
nikos_tapinos@brown.edu
https://vivo.brown.edu/display/ntapinos# 

IP Information
PCT/US2021/048671, filed September 1, 2021.

Publication
Zepecki JP, et al., Regulation of human glioma cell migration, tumor growth, and stemness gene expression using a Lck targeted inhibitor. Oncogene. 2019 Mar; 38(10):1734-1750. 
 

Patent Information: