Virus-like particles

In addition to their desired therapeutic effect, many drugs elicit serious adverse effects. Direct administration of a medicinal product at the target site can dramatically reduce the side effects. Several new active substances can be used only in this way.

The development of vaccines requires the design of vehicles that have high valence target structures on their surfaces (i.e. there are many of them) that are present in combined form.

Virus-like particles (VLPs) are biobased capsules that resemble viruses and have a wide range of applications. VLPs can arise in the process of virus replication as natural non-infectious by-products that contain no viral genetic material. Alternatively, VLPs can be produced by genetic engineering processes in which protein building blocks spontaneously assemble into hollow geometric structures.  

VLPs are ideal for packaging and targeted control of active substances (drug delivery) as a result of their ability to transport therapeutic agents in high concentration, with minimal side effects and in a targeted manner through intravenous routes.

Because of their stability, size and multivalency, VLPs also make an excellent basis for vaccines, for examples against viruses, which cannot be cultured or can only be cultured with diffculty in vitro, or against foreign proteins that are presented on the surface. Because of their biocompatibility and wide range of potential applications, the pharmaceutical industry has shown great interest in VLPs.

At present, the widespread use of VLPs is limited by the lack of standardized and effcient processes, which, much like a modular construction system, are suitable for producing a variety of different VLPs that can transport specifc loads to various target sites. Moreover, the purifcation steps of such a production process must be developed specifcally for each protein and VLP. Such a process that must be designed empirically and individually is time- and cost-intensive and therefore poses a challenge for production at an industry-scale.

In a new undertaking at the Fraunhofer IGB, we hope to develop a modular system as a platform technology for producing VLPs. A basic module structured with an internal capsule will be incorporated with a functional, variable and complex protein surface that can be used either for targeted control of VLPs (drug delivery) or for the development of vaccines.

For example, antibody fragments or antigens could be used to create a surface that is functional and multivalent. Because the basic module always remains unchanged and only the protein surface is confgured as needed, the production of VLPs, unlike current systems, can be standardized and hence would be reproducible and cost-effective.  

Non-enveloped viruses from the Caliciviridae family will be used as the base. We will develop a plasmid that allows the synthesis of the virus proteins – the capsules of these viruses consists of a single type of protein – in the yeast Saccharomyces cerevisiae. This organism has proven to be ideal for protein synthesis for pharmaceutical purposes because it generates few side effects and is cost-effective.

As “proof of principle”, VLPs that conduct active agents specifcally to surface markers of cancer cells via antibodies will be produced.

There is market demand for a modular system that uses a standardized process and has a wide range of potential applications. In addition to global corporations, SMEs in particular are sharing the pharmaceutical market for drug delivery methods and vaccine development.