Figure 1 Presentation of building blocks as a two-dimensional mosaic on the surface of nano-particles Figure 2 Binding of Mozaic nanoparticles to receptors on the cell surface Figure 3 Construction of drug molecules from building blocks, based on structures located on the surface of therapeutically active nano-particles
Mozaic is a revolutionary approach, developed in the UK, for creation of new therapeutic agents. Using the Mozaic technology, one can construct, out of basic molecular building blocks, structures which recognise specifically membrane receptors on the surface of cells. Binding to these receptors stimulates signalling events in the cells, up- or down-regulation their activities. The new structures generated can be employed as therapeutic agents in their own right, modifying the behaviour of diseased cells, or they can be used as targeting agents to carry cytotoxic drugs to tumour cells.
The key aspect of the Mozaic approach is that it presents small molecular building blocks (eg amino acids) on the surface of a type of nano-particle known as a lipid micelle. (see figure 1). The building blocks form a twodimensional dynamic fluid-mosaic array on the surface of the nanoparticle. Each nano-particle contains tens or hundreds of building blocks on its surface, so that many different structures can be formed when these building blocks come together. When a cell sees the nano-particle, a strong interaction can take place because the nano-particle has multiple “precursor epitopes” to which cell receptors can bind (figure 2). By presenting cells with various different nano-particles, each containing different combinations of building blocks, one can find out which combination has the strongest effect on a particular type of cell. This information is used to create a single molecule having a novel structure which interacts strongly with cells in vivo to exert a therapeutic effect (figure 3). The first generation of therapeutic molecules generated by Mozaic are self-associating peptides which can both up and down-regulate secretion from cells of cytokines such as TNF alpha. Other work in progress has resulted in structures which target to breast cancer cells, while further studies are directed towards modulating activity of cells involved in bone turnover. Mozaic Discovery Ltd employs a strategy of licensing its patented technology to partners in particular disease areas, and is working in collaboration with a number of pharmaceutical companies to bring these products to market.