Vector-payload complex generated by Vect-Horus are designed to display a dual function, namely i) target a specific cell-surface endocytic receptor expressed by target cells of a given pathophysiological tissue, and ii) deliver the therapeutic or imaging payload in the right subcellular compartment (biophase) in pharmacological/sufficient amounts.
Following engineering and release of high-quality vector-payload complex, Vect-Horus has developed various in vitro models to evaluate their properties and verify that each moiety of the complex retains its properties. Indeed, not only each vector-payload complex should retain the expected biological activity of the payload, but it should also retain full targeting potential. Because securing the transition from preclinical settings to the clinics is of paramount importance, the in vitro screening steps are conducted on rodent, non-rodent and human forms of the target receptor, using both acellular systems such as Surface Plasmon Resonance (SPR) and a variety of cell lines including those engineered by Vect-horus to express the receptors of interest.
Beyond these crucial initial validation steps, additional expertise is often required to better understand and evaluate the fate of the vector-payload complex once endocytosed into brain endothelial cells (ECs) or into any target cell type of the body. Over the years Vect-Horus has thus developed the following expertise:
- In vitro BBB models: Vect-Horus has developed and undergoes continuous optimization of in vitro BBB models based on primary rat endothelial cells that recapitulate the main characteristics of the in vivo BBB, taking into account the neurovascular unit to predict brain exposure of molecules of interest.
- Intracellular trafficking in relevant non-endothelial cellular models : the rational engineering of new vector-payload complex and early investigation of their intracellular trafficking profile in vitro is of paramount importance for Vect-Horus to i) understand the target engagement modalities of the vectors we develop, and ii) allow selection of candidates with optimal intracellular delivery potential in the appropriate subcellular compartment.