Virus-like particles - Biocontainer for drug transport and vaccination

In addition to the desired therapeutic effect, a large number of drugs also cause severe side effects. A targeted application of the drugs directly at the site of action can greatly reduce the side effects. Some new active substances can only be used in this way.

In vaccine development, vehicles are required that present target structures on their surface in a highly valent form, i.e. in large numbers, and in combined form.

Virus-like particles (VLP) are bio-based capsules that mimic viruses and can be used in a variety of ways. VLPs can be produced during virus replication as natural non-infectious by-products that do not contain a virus genome. Alternatively, VLPs can be produced by genetic engineering, whereby protein building blocks spontaneously assemble into a geometric structure with a cavity.

VLPs are suitable for the packaging and targeting of active ingredients (drug delivery) because they can transport therapeutic agents in high concentrations, with few side effects and targeted intravenously.

Due to their stability, size and multivalence, VLPs are also excellently suited as a basis for vaccines, for example against viruses that cannot or can only with difficulty be cultivated in vitro, or against foreign proteins that are presented on the surface. Due to their biocompatibility and diverse application possibilities, the pharmaceutical industry is showing great interest in them.

The broad use of VLPs is currently limited by the lack of standardized and efficient manufacturing processes for bringing different VLPs with specific loads to different sites of action, similar to a modular system. In addition, the purification steps in particle production must be developed specifically for each protein or VLP. This empirical and individually adapted approach is time and cost intensive and thus a challenge for industrial production.

In a new project at Fraunhofer IGB we want to develop a kind of modular system as a platform technology for the production of VLPs. A basic module with an inner capsule structure will be genetically combined with a functional, variable and complex protein surface, which will be used either for target control of VLPs (drug delivery) or for vaccine development.

Antibody fragments or antigens, for example, can be used for multivalent functionalisation of the surface. Since the basic module always remains unchanged and only the protein surface is specifically designed, the production of VLPs can be standardised in comparison to current systems and thus be reproducible and cost-effective.

Envelope free viruses of the family Caliciviridae are used as a basis. For the synthesis of VLPs in baker's yeast (Saccharomyces cerevisiae) plasmids were developed which code for variants of the viral proteins. Baker's yeast is particularly well suited for the production of VLPs, as proteins for pharmaceutical applications can be produced in this organism with few side effects and at low cost.

A basic VLP structure has already been successfully produced and characterised in this way. This provides a system for the expression and isolation of native caliciviral VLPs so that downstream processing can be established. The aim is to establish an efficient and cost-effective process on the basis of these VLPs, which will enable the production of such biocontainers in large quantities and with high purity and homogeneity.

A modular system and a correspondingly standardized process has broad application potential and is in demand by the market. In addition to globally operating groups, SMEs in particular share the pharmaceutical market for drug delivery and vaccine development.

We would like to thank the Fraunhofer-Gesellschaft for funding the work on establishing virus-like particles as part of the program "Mittelstandsorientierte Eigenforschung (Mef)" under the project title "Virus-like Particles - Biocontainer for drug transport and vaccination".