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Microvesicle-inspired drug delivery systems

Objective

Current state-of-the-art drug carrier systems deliver new ‘biological drugs’ (like proteins and nucleic acids) poorly to the target site. This is something I daily experience in my research on delivery of small interfering RNA. The in vivo challenges are threefold:
• Biological drugs are fragile molecules (subject to degradation and denaturation)
• They need to gain access to the target site
• They need delivery to a specific cell type and even to a specific subcellular location to be active.
Recent research points out an endogenous communication system transporting proteins and nucleic acids between cells, outperforming current synthetic drug delivery systems. These carriers, known as microvesicles, appear Nature’s choice for delivery of biologicals and have created excitement in the research community. Microvesicles encompass a variety of submicron vesicular structures that include exosomes, shedding vesicles, and microparticles. The lipids, proteins, mRNA and microRNA delivered by these microvesicles change the phenotype of the receiving cells. Microvesicles appear to play an important role in many disease processes, most notably inflammation and cancer, where their efficient functional delivery of biological cargo contributes to the disease progress. Up to now, most research addresses the role of microvesicles in cell biology. At the same time, surprisingly little is known about their in vivo kinetics, targeting behavior and tissue distribution from a drug carrier standpoint.
The aim of my proposal is to design and develop microvesicle-inspired drug delivery systems to improve targeting and delivery of biological drugs.
The work plan is divided into two approaches:
1-A synthetic approach based on liposomes or isolated microvesicle constituents
2-A biological approach based on biotechnologically-engineered and cell-produced microvesicles.
The results of this research are expected to improve insights into in vivo behavior of microvesicles and the critical molecules that trigger their delivery and targeting success. It should also be clear which of the two approaches is best suited for the production of pharmaceutically acceptable microvesicle-mimics. Finally, the research should result in a prototype microvesicle-inspired carrier. These results can form the basis for an attractive new generation of microvesicle mimicking drug delivery systems.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/biological sciences/cell biology
  • /natural sciences/biological sciences/biochemistry/biomolecules/nucleic acid

Call for proposal

ERC-2010-StG_20091118
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Address
Heidelberglaan 100
3584 CX Utrecht
Netherlands
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 132 222
Principal investigator
Raymond Michel Schiffelers (Dr.)
Administrative Contact
Susan Zwaagstra (Ms.)

Beneficiaries (2)

UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Netherlands
EU contribution
€ 1 132 222
Address
Heidelberglaan 100
3584 CX Utrecht
Activity type
Higher or Secondary Education Establishments
Principal investigator
Raymond Michel Schiffelers (Dr.)
Administrative Contact
Susan Zwaagstra (Ms.)
UNIVERSITEIT UTRECHT

Participation ended

Netherlands
EU contribution
€ 205 778
Address
Heidelberglaan 8
3584 CS Utrecht
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Rinske Kok-Baan, De (Ms.)