Researchers at Colorado State University have developed resurfaced cell-penetrating nanobodies that can enter living cells efficiently. These engineered proteins act as flexible scaffolds for discovering therapies that target disease-related molecules inside cells. Unlike most protein therapeutics, these nanobodies can reach intracellular receptors that were previously inaccessible. This platform increases the number of biological targets available for drug discovery and research.
Many diseases are driven by proteins inside cells, but most protein-based drugs cannot cross the cell membrane. As a result, current biologics interact with proteins on the cell surface, which limits treatment options. Nanobodies are small, stable proteins that can bind targets with high specificity and are easily modified. Making them able to enter cells opens new possibilities for developing therapies and studying intracellular processes.
This platform uses resurfaced nanobodies engineered with positive surface charges to help them pass through the cell membrane. Nanobodies are small, robust antibody-derived proteins with strong binding ability. By modifying the surface while keeping their shape and stability, researchers created nanobodies that can enter cells and reach the cytosol without losing function.
These nanobodies can be used as general scaffolds. They can be screened or modified to bind different intracellular disease targets. Their stability and adaptability let researchers apply standard protein engineering techniques to discover new therapeutics. This platform allows drug discovery for targets that were previously hard to reach and support both lab-based (in vitro) and living organism (in vivo) testing.
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Brian McNaughton
Virginia Bruce
Steve Foster
Steve.Foster@colostate.edu
970-491-7100