Nanoparticles for topical administration of siRNA to the airways for cystic fibrosis therapy (360G-Wellcome-094348_Z_10_Z)
We are assessing nanoparticle formulations for siRNA therapy of cystic fibrosis. Initial experiments on siRNA delivery to primary airway epithelial cells will characterise ICAM-1 cell receptor targeting and subsequent intracellular trafficking. ICAM-1 receptor is an interesting target, since it is also exploited by rhinovirus for epithelial cell binding and entry in the airways. ICAM-1 targeting will be assessed in cell binding and transfection studies then fluorescently labelled particles will be characterised for intracellular trafficking by confocal microscopy. Knockdown studies will focus on the endogenous housekeeping gene GAPDH. Particles will be analysed for their biophysical properties before and after nebulisation to assess their in vivo potential. In vivo delivery will be performed to assess delivery strategies, such as dosage and repeat delivery frequency. Safety studies in terms of lung damage and inflammation will be evaluated. We will then transfect ENaC siRNA into normal and CF epithelial cells which will be characterised by qPCR and Western blotting for the three different chains of ENaC. The physiological analysis will focus on fluid absorption, electrophysiology, mucus production and ciliary mobility. Finally, we will explore the combination affect of gene therapy, delivering CFTR, and siRNA on cell physiological parameters.
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Grant Details
Amount Awarded | 247994 |
Applicant Surname | Hart |
Approval Committee | Physiological Sciences Funding Committee |
Award Date | 2011-03-15T00:00:00+00:00 |
Financial Year | 2010/11 |
Grant Programme: Title | Project Grant |
Internal ID | 094348/Z/10/Z |
Lead Applicant | Dr Stephen Hart |
Other Applicant(s) | Dr Robin McAnulty |
Partnership Value | 247994 |
Planned Dates: End Date | 2014-08-31T00:00:00+00:00 |
Planned Dates: Start Date | 2011-09-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |