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Controlled fusion of liposomes and cells: a new pathway for direct drug delivery (DirectDelivery)
Start date: Oct 1, 2009, End date: Sep 30, 2014 PROJECT  FINISHED 

Inspired by the natural membrane fusion machinery, the aim of this research line is to design a synthetic analogue in order to: 1) Understand the process of the peptide-controlled fusion of two membranes at the atomic, molecular and mesoscopic level. 2) Developing a new generic method for the controlled delivery of any (bio)molecule directly into the cytoplasm of a cell thereby omitting endocytotic pathways. This new paradigm opens many new applications in the fields of functional proteomics, genomics and siRNA-technology. Studying, imitating and dissecting processes from Nature and applying the underlying principles has been highly successful approach for many years and opened up new lines of research and applications which were previously unimagineable. Examples are the aptamer and antibody technology. I will use this learning-from-Nature approach to design synthetic analogues of the membrane fusion machinery to create new functions and/or applications which are currently non-existent. Membrane fusion is a key process in all living cells as it facilitates the transport of molecules between and within cells. A primary mechanism by which molecules are conveyed to the appropriate location is to encapsulate them in liposomes that deliver the cargo by fusing with the lipid membrane of the target cell or compartment. I will use synthetic analogues of the membrane fusion machinery to induce the controlled fusion between 1) specific liposomes and 2) liposome-cell. This approach opens up a new paradigm for the direct introduction of (bio)molecule into the cytoplasm of living cells omitting the endocytotic pathways for which the applications are only limited by one s imagination.
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