Capsulution and Qiagen combine nanotechnology, oligonucleotides

The co-operative research agreement between Capsulution and Qiagen, German subsidiary of the Dutch supplier of sample and testing technology and products, will "make use of the synergies arising between programmable biomolecules and the latest developments in nanotechnology", the companies said.

The project, which involves coupling oligonucleotides to nanocapsules customised with Capsulution's proprietary LBL technology to create targeted drug-delivery vehicles or diagnostic kits, is supported with funding of €1.23m from the German Ministry of Science and Technology's nanobiotechnology sponsorship programme.

Also participating are the faculties of chemistry and biology at Berlin's Humboldt University and the faculty of biotechnology at Martin Luther University in Halle-Wittenberg.

Capsulution's LBL (meaning "layer by layer") technology is a tool for making multifunctional nano- and micron-sized capsules invisible to the human eye.

Depending on the intended application, any size of capsule can be produced and endowed with "almost any pharmaceutical, biochemical, electrical, optical or magnetic property" , the company says.

In the encapsulation process, polyelectrolyte molecules are applied layer by layer, creating an ultra-thin polymer film.

The coating is propelled by electrostatic gravities, with each new layer given the opposite charge of the previous layer.

The resulting capsule walls, which generally comprise four to 20 polyelectrolyte layers with a total thickness of 8-50 nm, can perform additional functions such as providing a surface for antibodies to dock on to.

The main focus of the joint project with Qiagen is on rapid diagnostics, using the attached oligonucleotides as probes for complementary DNA or RNA.

Applying the LBL technology, the researchers will construct nanoparticles consisting of a magnetic core and a functionalised shell.

Nucleotide fragments will then be coupled to the modified surface of the LBL capsules, so that they "stick out of the particles like hooks", Capsulution and Qiagen explained.

The role of the oligonucleotides will be to attract complementary nucleic acid filaments into the testing samples, with the magnetic core serving to target the nanoparticles more precisely.

Fluorescence Resonance Energy Transfer (FRET) technology will be used to provide evidence of a successful hybridisation event.

The project group wants to enhance the sensitivity of this evidence by working one of the two fluorescent dyes involved into the LBL capsule surface.

The aim of this research is to facilitate the discovery of genetic markers for viruses or diseases, without any need for concentration, purification or amplification of the targeted biomolecule or gene.

"We want to develop a method which delivers accurate results, which is reasonably priced and can be carried out by less specialised personnel in the most diverse of laboratories worldwide," commented Dr Loanna Andreou, senior scientist for research and development at Qiagen.

The therapeutic potential of this technology consists in using the oligonucleotides to help achieve precise cell targeting of drug substances that need to be delivered without any leakage en route .

The nanocapsules would serve as delivery vehicles or even 'Trojan horses' that could penetrate cell barriers, with the encapsulated drug released externally or internally only when it had locked onto the target cell.

This would be an "enormous" therapeutic advance, particularly in some forms of cancer such as leukaemia, where the technology could create treatments virtually devoid of side-effects, the research partners claimed.

Some 60 per cent of Capsulution's resources are already committed to pharmaceutical projects centred on drug delivery, with some of these in preclinical studies, the company noted.

A more immediate priority in the collaboration with Qiagen, though, will be enhancing the stability of the attached oligonucleotides, which are highly sensitive to enzymatic degradation, Capsulution said.

Any intellectual property on new products arising from the collaboration will be shared between the partners, including the participating universities, although enhancements of existing proprietary technology - for example, of Capsulution's LBL system - will remain the property of the original owner.

This is an important facet of the project, Capsulution pointed out, as it enables the company to develop a "family of applications" for the LBL technology, some of them outside the scope of the collaboration.

Marketing exclusivity has been left open between Capsulution and Qiagen for the time being.