Delivery of siRNAs to hematopoietic stem cells using nanoparticles

Objective

RNA interference (RNAi) is a ubiquitous and highly specific, endogenous, evolutionarily conserved mechanism of gene silencing. Since the discovery that RNAi occurs in mammalian cells, RNAi has emerged as a powerful tool for elucidating gene function and identifying potential drug targets. Harnessing RNAi holds enormous promise for therapeutic use for diseases that have proven difficult to treat with conventional drugs. RNAi can also be exogenously activated either by transducing cells with vectors to express small hairpin RNAs (shRNA) or by introducing already processed short double-stranded RNAs (siRNAs) into the cytoplasm of cells.
To realize the potential of siRNAs for in vivo drug discovery and therapy there is a need to overcome the considerable hurdle of intracellular delivery across the plasma membrane. siRNAs are not taken up into most cells in vitro in the absence of a transfection reagent. For many cells, mixing siRNAs at nanomolar concentrations with a lipid transfection can efficiently induce gene silencing. However, some important cells, including primary lymphocytes and hematopoietic stem cells, remain highly resistant to lipid transfection schemes.
We have recently developed nanoparticles that target integrin b7 that is expressed on leukocytes involved in gut inflammation. Using this approach, we revealed cyclin D1 to be a potential anti-inflammatory target in inflammatory bowel diseases.
The goal of this proposal is to explore the hypothesis that targeted nanoparticles entrapping siRNAs can be developed to induce in vivo gene silencing in hematopoietic stem cells. Using this strategy, we plan to identify key genes responsible for pluripotent hematopoietic stem cells (pHSC) self-renewal properties. This will provide a powerful technique to investigate the contribution of individual genes in maintaining the phenotypic and functional properties of pHSC, and ultimately may provide a way to improve engraftment during bone marrow transplantation.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.

• medical and health sciences basic medicine pharmacology and pharmacy drug discovery
• medical and health sciences clinical medicine gastroenterology inflammatory bowel disease
• medical and health sciences medical biotechnology cells technologies stem cells
• natural sciences biological sciences genetics RNA
• medical and health sciences clinical medicine transplantation

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

• FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants"

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-IRG-2008
See other projects for this call

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IRG - International Re-integration Grants (IRG)

Coordinator