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Studies to date have shown that X-entry transports functional cargoes across cell membranes, including large molecules inhibitory peptides, functional antibodies, and an enzyme.
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Summary: The plasma membrane of cells is poorly permeable to both drugs and proteins (including DNA), whilst DNA is also a very inefficient translocator within cells. Thus, delivery of biologically active molecules into cells is very difficult. By attaching a cell-penetrating peptide (CPP), either covalently or non-covalently, the intracellular delivery of biomolecules and proteins can be significantly improved. A novel CPP designated X-entry derived from the X-protein of the hepatitis B virus, which is essential for virus infection was identified by Associate Professor Geoff Krissansen at The University of Auckland. X-Entry is a platform technology that enables delivery of a variety of biological cargo molecules into cells, including therapeutic agents.Studies to date have shown that X-entry transports functional cargoes across cell membranes, including large molecules inhibitory peptides, functional antibodies, an enzyme, oligonucleotides and siRNAs. We have also undertaken biodistribution studies with X-entry alone, and attached to an enzyme cargo. These studies showed highest level of X-entry uptake by the heart, lung, liver, kidney, small intestine, spleen and stomach. Applications • Delivery of large molecules into cells to reach an intracellular target • Delivery of small molecules that are not efficient at getting into cells • Intracellular delivery of therapeutic agents to combat disease • Intracellular protein replacement due to defective genes • Delivery of imaging agents into cells • Research Tool Key Aspects • It is only taken up by adherent cells, which prevents X-entrybeing “mopped up” by blood cells following injection, A cell penetrating peptide delivery platform thereby enabling more efficient targeting of tissues thus improving efficacy, while limiting potential off target toxicity. • It is small compared to other known peptides - only 7 aminoacids in length therefore costs of goods are lower. • Uptake is more controllable as uptake is specifically via syndecan-4 (and potentially other syndecans), whereas otherCPPs use syndecans and a multitude of other mechanisms. • It is taken up into the cytoplasm and nucleus of the cell.