Biond has developed INspire, an intracellular delivery platform for Biologics. This platform technology delivers various types of protein-based biologics, e.g. antibodies, nanobodies or enzymes, inside cells, allowing to drug intracellular-targets currently considered “undruggable”. Using INspire, we have successfully delivered agents targeting KRAS, BRAF and HPV-E7, overcoming the fundamental challenges of the intracellular delivery of biologics. We have further showed intracellular functionality of all delivered agents
The INspire delivery technology is based on a chemically modified carrier protein which is further chemically conjugated to a biologic payload (antibodies, etc.). The carrier’s modification is characterized by a high and concentrated positive charge that enables cell internalization and efficient endosomal escape, delivering the payloads to the cytoplasm. The positive charges are further transiently masked, neutralizing the positive charges and adding negative charges, to enable clinically relevant PK and biodistribution.
Delivering biologics to the tissue of interest and internalization of the biological payload into cells is a major challenge. INspire uses positive charges that are transiently masked by negative charges that are further removed in Low pH environments, such as can be found in the Tumor Microenvironment (TME) and inflammation sites. This design enables effective tissue targeting, intracellular delivery to target cells and endosomal escape
The INspire transient masking enables the carrier-payload conjugates to exhibit efficient pharmacokinetics and biodistribution profiles (1&2). The low pH environment of tumors selectively removes the masking (3), enabling the conjugates to commence their cell internalization process (4), only in this target tissue. The INspire conjugates can now cross the cell membrane (5), escape the endosomes (6&7) and release their payloads in the cytoplasm (8) to exert their functional activity (9).
Confocal microscopy images (X63) of B16 tumor tissue from C57BL mice, 6 hours after injection of fluorescently labeled transient-masked carrier (left), non-transient masked carrier (middle) and non-masked carrier (right). Carrier staining (Red); Nuclear staining (Blue).
Athymic nude mice inoculated with HeLa-GFP cells. Red – Carrier, Blue – Nuclei of all cells
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