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.

Trehalose, a Novel mTOR-independent Autophagy Enhancer, Accelerates the Clearance of Mutant Huntingtin and α-Synuclein

“…Extracellular trehalose is likely acting in the cytosol in the same compartment(s) as the trehalose in the stable cells. There are many precedents for cells taking up extracellular material that does not readily cross cell membranes by pinocytosis or endocytosis and then releasing it into the cytosol, including MHC class II antigen presentation (42), and DNA transfection methods (43,44). Thus, it is entirely plausible that high concentrations of extracellular trehalose can act via effects in the same cytosolic compartments as plasmidsynthesized trehalose, outside of membrane-bound pinosomes or endosomes.…”

Nanovehicular Intracellular Delivery Systems

“…To enable this, as peptide-nucleic acid complex with functional properties is hybridized to DNA plasmid, providing better formulation stability and minimal inactivation. 383 The functional element can include localization or targeting signals.…”

20 Years of Hypertension Research using Genetically Modified Animals: No Clinically Promising Approaches in Sight

“…However, it is clear that all these vectors are still not safe enough to be used in humans: cytotoxicity is a risk factor for all vectors and, in addition, cancer and mutations are risks for all viral vectors (Raizada and Der Sarkissian, 2005;Heistad, 2006). Gene therapy via gene transfer using viral or nonviral vectors has only been performed in animal experiments to date (Simonson et al, 2005;Nakamura et al, 2006). With regard to primary hypertension, such approaches still have no discernable clinical impact (Puddu, 2006).…”