Delivery of therapeutic molecules into cells is very difficult as the plasma membrane of cells is poorly permeable to biologically active molecules. Research at The University of Auckland has identified a novel five amino acid cell penetrating peptide designated ‘X-entry’, derived from the X-protein of the hepatitis B virus. In vitro studies have shown that X-entry can enter a variety of cells. X-entry was able to enter all adherent cell lines examined. In contrast, it is not able to permeate non-adherent cells, including primary blood lymphocytes. In vitro studies to date have demonstrated that X-entry can transport functional cargoes into cells. Thus far, X-entry has been shown to carry inhibitory peptides, antibodies, oligonucleotides and siRNA into cells. Exactly how X-entry passes through the plasma membrane of cells is still not fully understood. Cell uptake was concentration and temperature dependent, the latter supports an energy-dependent endocytic process. However, further work is required to delineate the cellular requirements for peptide entry. Investigations to be conducted in early 2012 will determine the pharmacokinetic properties of X-entry in a living animal, namely in mice. Intravenous, subcutaneous, intraperitoneal and oral routes of delivery will be examined.
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A patent application (NZ 586074) was filed on 10 June 2010 with a provisional specification. The PCT/NZ2011/000102 was filed on 10 June 2011. The patent application covers novel peptides derived from the X protein and functional equivalents to these defined peptides and the use of such peptides as cell membrane permeable carriers for compounds (including other peptides and peptidomimetics). A patent application (NZ 593396, "Peptides, constructs, and uses therefore) was filed in 2011 with a provisional specification.
Proof of Principle - Laboratory demonstration of principle only