From molecular targets to cellular targets

With the development of molecular biology, we understood that changes in sequence and expression of genes can cause several diseases. As such, from approaches targeting “molecules” such as therapies using small molecules and antibody therapy, a new approach targeting “cells” such as gene supplementation, gene editing, and cell transplantation have been developed.

However, for such strategies to be effective, we need to address their targetability to specific cells.

In gene therapy, we must consider unexpected side-effects on healthy cells, which may diminish a treatment approach due to safety concerns; lowering efficiency and efficacy. Despite the causes of a disease being identified and viable approaches being developed, the therapeutic applicability of such methods can be limited due to low specificity.

Furthermore, low specificity also has negative effects on the cells of a high enough purity for transplantation, limiting the usefulness of transplantation in clinical settings, as it can be difficult to guarantee that transplanted cells will not evolve into tumors.

This means there is a growing need for a technology that allows us to generate, treat and target “specific cells”.

The RNA Switch Technology

We have developed “RNA Switches” as a means of addressing these concerns.
RNA Switches are a specifically designed synthesized messenger RNA that:
1, Identifies highly active micro RNAs (miRNAs) in target cells
2, Regulates protein expression in response to the activity of these specific miRNAs
There are around 2,600 miRNAs identified in humans, and their expression and activity are known to vary among cell types and phenotype. By taking advantage of miRNA’s characteristics and RNA Switches, we can develop a platform to regulate exogenous transgene, such as therapeutic gene in gene therapy and exogeneous transcriptional factor in cell therapy.

Source) Miki et al. Efficient Detection and Purification of Cell Populations Using Synthetic MicroRNA Switches. Cell Stem Cell. 2015

How do RNA Switches work?

RNA Switches take advantage of the innate capability of miRNA to specifically inhibit and degrade specific Messenger RNAs (mRNAs). At aceRNA Technologies we are using our patented technology to develop “OFF” and “ON” RNA Switches. “OFF” RNA Switches are deactivated when they bind to a specific intracellular miRNA. Likewise, “ON” RNA Switches are activated when they bind to a specific intracellular miRNA. Both types of switches can be designed to bind to any specific one from >2,600 known miRNAs.

What can we do with RNA Switches

RNA Switches can be employed in drug development in fields such as Regenerative Medicine and Gene Therapy.

In cell transplantation approaches, RNA Switches can be utilized in the generation of cell types difficult to generate under conventional protocol. In Gene Therapy, RNA Switches can be utilized in the fine tuning of expression of therapeutic transgene in both virus-based and mRNA-based approaches. At aceRNA Technologies we are especially focused on the development of mRNA-based drugs. By exploiting RNA design technologies, we are actively researching technologies of regulating gene expression according to cell type and phenotype, with the goal of developing innovative drugs using “Smart mRNA”. Development of smart mRNA-based therapies enable us to reduce unexpected effects of the treatment on non-target cells, thus reducing the possibility of undesired side-effects. Such drugs have a potential of enabling new revolutionary approaches for treating diseases.