Safety evaluation of Bcl2L12-targeting SNAs in non-human primates

Project: Research project

Project Details


The Mirkin group has developed unique oligonucleotide containing compounds, called Spherical Nucleic Acids (SNA) constructs (Figure 1), which due to their spherical presentation of nucleic acids, have many ideal properties for oligonucleotide-based drug development. The constructs have unprecedented abilities to enter cells, organs and tissues without the need for additional physical or chemical methods. SNAs can be specifically designed to allow for modulation of pathways that are central to combating a broad array of diseases, including skin conditions, cancer, and neurological disorders. In collaboration with the Stegh group, these SNA constructs have been shown to cross the blood-brain-/blood-tumor barriers when injected intravenously in Glioblastoma- bearing mice, reduce tumor burden and increase their survival.
Delivery across the blood-brain barrier has remained a formidable obstacle to gene regulation and conventional chemotherapies. SNA constructs have the potential to overcome this obstacle. SNA constructs can pervasively infiltrate the brain, selectively accumulate in tumors via enhanced permeability of the tumor-associated vasculature, trigger intratumoral knockdown of Glioblastoma oncogenes, e.g. Bcl2Like12 (Bcl2L12), reduce tumor burden and significantly extend the lives of tumor-bearing mice. This ability to deliver targeted therapeutics across the blood-brain-barrier and throughout the brain is a groundbreaking development for neurological therapies, which was recently published in Science Translational Medicine (Jensen et al., 2013; Cover of Science Transl. Med. Oct 30; 5(209): 209ra152). This study has been attracting significant media (US News, FoxNews, Genetic Engineering & Biotechnology News, WGNTV, Chicago Sun-Times, Chemical & Engineering News, Neurology Today) and patient attention.
These detailed physico-chemical, in vitro and in vivo efficacy studies demonstrated the enormous potential of these nanoconstructs for the treatment of patients with GBM. We are poised to take next logical step to enroll siL12-SNAs into first in-human phase 0 clinical trials in 2015, i.e., safety studies in non-human primates required by the FDA as mentioned in our pre-IND discussion.
Effective start/end date8/1/1410/31/14


  • Stephen M. Coffman Charitable Trust (SMCCT7142014)


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