Cell penetrating peptide

Cell penetrating peptide

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.

Objective

UniServices is seeking investment and partnerships with industry.

Unique Selling Propositions
  • X-entry holds two major competitive advantages over incumbent cell penetrating peptides:
  • X-entry holds a therapeutic advantage in that it is not taken up by non-adherent cells, hence will not be sequestered and diluted by blood cells following injection, thereby enabling more efficient targeting of tissues
  • X-entry is the smallest known carrier peptide, only five amino acids in length. This confers the advantage of low cost manufacture
Applications
  • X-entry maybe utilised to improve existing therapies and/or develop new therapies targeting previously "undruggable" intracellular targets. X-entry may be of high value in gene therapy approaches by significantly improving delivery oligonucleotide constructs.
IP Strategy

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.

Project Status

Proof of Principle - Laboratory demonstration of principle only