Celsion’s TheraSilence platform is focused on delivering synthetically generated short interfering RNA (siRNAs), microRNAs (miRNAs), microRNA mimics, and related molecules that can regulate protein expression by exploiting endogenous cell mechanisms. These mechanisms are believed to have potential for creating a new class of therapeutics that are safer and more efficacious for many types of disease, including those that are not currently “druggable” by conventional means. TheraSilence is based on RNA interference (RNAi), a naturally occurring process in which specific messenger RNA is inhibited or destroyed, thus regulating protein expression. The company has developed several classes of proprietary carriers that can efficiently deliver the siRNAs to the cytoplasm of many types of cells, both in vitro and in vivo.

Addressing the primary obstacle to nucleic acid–based therapeutics

TheraSilence technology addresses the primary obstacle to nucleic acid–based therapeutics—efficient delivery to target cells. Specifically, a delivery system must protect the RNAi from nuclease degradation, transfer the molecule across the cellular membranes, and release it so that it can be available to the endogenous RNA silencing machinery. Celsion has developed proprietary, novel structures that are: (1) able to interact with the RNAi molecules, forming protective nanoparticles that can be readily taken up into cells; (2) Chemically flexible and amenable to attachment of tissue-targeted ligands, in vivo stabilizing agents, and other functional moieties which can tailor a formulation for a particular application and delivery modality.

We believe that these features can provide high specificity for RNAi delivery to select tissue, enhance stability, and reduce in vivo toxicity.

Proof-of-concept in lung tumors

In-vivo proof-of-concept studies of our most advanced system have shown the ability to deliver RNAi molecules specifically to pulmonary vasculature following intravenous administration. Using this delivery system we have been able to show in mice that delivery of a siRNA molecule targeting receptor 2 of vascular endothelial growth factor (VEGF), a protein critical for angiogenesis, can significantly inhibit lung tumor growth.

TheraSilence Preclinical Studies

Lung cancer preclinical studies: In a mouse lung tumor model, vascular endothelial growth factor receptor-2 (VEGFR-2) siRNA was formulated with TheraSilence LNPs. Intravenous treatment resulted in a significant decrease in VEGFR-2 transcript and a significant reduction in lung tumors.