title: Bioplex technology: novel synthetic gene delivery pharmaceutical based on peptides anchored to nucleic acids.
abstract: Non-viral gene delivery is an important approach in order to establish safe in vivo gene therapy in the clinic. Although viral vectors currently exhibit superior gene transfer efficacy, the safety aspect of viral gene delivery is a concern. In order to improve non-viral in vivo gene delivery we have designed a pharmaceutical platform called Bioplex (biological complex). The concept of Bioplex is to link functional entities via hybridising anchors, such as Peptide Nucleic Acids (PNA), directly to naked DNA. In order to promote delivery functional entities consisting of biologically active peptides or carbohydrates, are linked to the PNA anchor. The PNA acts as genetic glue and hybridises with DNA in a sequence specific manner. By using functional entities, which elicit receptor-mediated endocytosis, improved endosomal escape and enhance nuclear entry we wish to improve the transfer of genetic material into the cell. An important aspect is that the functional entities should also have tissue-targeting properties in vivo. Examples of functional entities investigated to date are the Simian virus 40 nuclear localisation signal to improve nuclear uptake and different carbohydrate ligands in order to achieve receptor specific uptake. The delivery system is also endowed with regulatory capability, since the release of functional entities can be controlled. The aim is to create a safe, pharmaceutically defined and stable delivery system for nucleic acids with enhanced transfection properties that can be used in the clinic.
authors.affiliation: Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Stockholm, SE-141 86 Stockholm, Sweden. oscar.simonson@crc.ki.se
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Simonson
authors.forename: Mathias G
authors.initials: MG
authors.lastname: Svahn
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Törnquist
authors.forename: Karin E
authors.initials: KE
authors.lastname: Lundin
authors.forename: C I E
authors.initials: CI
authors.lastname: Smith
mesh_terms: D000818:Animals; D001212:Asialoglycoproteins / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D020650:Combinatorial Chemistry Techniques; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry*; D016503:Drug Delivery Systems; D015316:Genetic Therapy; D006801:Humans; D008099:Liver / Q000187:drug effects; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D001212:Asialoglycoproteins; D028861:Nuclear Pore Complex Proteins; D020135:Peptide Nucleic Acids; D010455:Peptides; D004247:DNA