Magnetic Field Emulations of Small Inhibitor RNA: Effects on Implanted GL261 Tumors in C57BL/6 Immune Competent Mice

Abstract

Background: EMulate Therapeutics has developed a system for emulating the effects of small solvated molecules via their magnetic field recordings. Recordings of magnetic field emissions of select small inhibitor RNAs (siRNAs; murine targeting CTLA-4 and murine targeting PD-1) were tested on C57Bl/6 mice implanted subcutaneously with the GL261 murine tumor cell line. Methods: A signal composed of the concatenated recordings of siRNA molecules targeting the murine CTLA-4 and PD-1 receptors (labeled A2) was used in immune competent C57Bl/6 mice. The mice were flank implanted with the murine glioblastoma cell line GL261. Mice were exposed to the signal continuously (24 hours a day) until tumor volumes reached the designated volume limit. Tumors were excised and analyzed via PAGE/Western blot for the expression of CTLA-4, PD-1, Ki67, Caspase 3, CD4 and CD8. Terminal blood draws were used for CBCs. Results: We report the down regulation of the checkpoint inhibitors CTLA-4 in the exposed mice. Significant tumor volume reduction was observed in mice exposed to the siRNA signal compared to control mice; no adverse events were recorded. Cell blood counts (CBC) and protein expression patterns were observed to correlate with the expected function of protein expression inhibition of the targets. Conclusions: The effect of the magnetic field emission targeting CTLA-4 and PD-1 demonstrates the ability to emulate the effects of siRNA and support previously published work using this technology.