Introgen Adapts Nanotechnology for Protein Delivery

Introgen Therapeutics (Austin, TX, www.introgen.com) has acquired a new license from the University of Texas MD Anderson Cancer Center for a nanotechnology delivery system, covered by US Patent application 20060251726, dated November 9, 2006, for proteins and peptides.

The delivery system has previously shown efficacy in animal models for the delivery of the FUS1 tumor-suppressor gene for the treatment of non-small cell carcinoma. The delivery platform is currently in Phase 3 trials for delivery of the p53 gene, also for the treatment of non-small cell carcinoma.

The newly licensed delivery system is also a lipid-based nanoparticle, but is instead used to deliver proteins and peptides. To facilitate delivery, the researchers reduced the FUS1 protein to a short polypeptide sequence of approximately 20 amino acids. The amino acids, in turn, are modified by the addition of a chemical moiety that facilitates cellular uptake. The chemical moiety added is a C.sub.4-C.sub.18 fatty acid, preferably stearate or myristate. “The fatty acid on the outside of the amino acid makes the protein more lipophilic, so it can cross the membrane more readily,” says David Parker, PhD, senior vice president of intellectual property at Introgen.

“This technology expands our current platform from being a gene-delivery platform into the realm of protein delivery,” says Parker. “And we’re always interested in ultimately developing an intravenous drug. Currently, our Advexin and mda-7 products are in the clinic in the mode of intra-tumoral injection. So the FUS1 nanoparticle program takes us into the intravenous administration realm.”

The researchers don’t know yet how large a molecule can be delivered using this technology; they will focus on this particular peptide first. The patent refers to peptides up to 100 amino acids in length, but indicates that the preferred size is 10 residues.