Selectively expressed RNA molecules as a versatile tool for functionalized cell targeting
Exact targeting of specific mammalian cell types or diseased cells is one of the most urgently needed prerequisites for a new generation of potent pharmaceuticals. Different approaches have been pursued, failing mainly due to a lack of specific surface markers in most cases. Developing a novel RNA-based methodology, we can now ensure exact cell targeting and simultaneously combine this with selective expression of effector proteins, thereby functionalization of the target cell for therapy, diagnostics or cell steering. The specific combination of the molecular properties of antisense technology and mRNA therapy with functional RNA secondary structures based on Nano-DMS-MaP analysis allowed us to develop selectively expressed RNA molecules for medical applications. These so-called seRNAs remain inactive in non-target cells and are only activated by partial degradation to induce translation in preselected cell types of interest. Cell type specificity and type of functionalization are easily adaptable based on a simple modular system. In proof of concept in vitro and in vivo studies we used seRNAs as a highly selective platform technology for powerful cell targeting. We effectively treat breast tumor cell clusters in mixed cell systems and reduce early brain tumors of mice without detectable side effects with just a single treatment. Our data open up new potential avenues for various therapeutic applications. Overall design: Nano-DMS-MaP analysis of seRNA. Selective and non-selective constructs we transfected into cells. RNA structure was determined by Nano-DMS-MaP probing.