RESUBMISSION : DNA hybridisation-mediated vesicle fusion - kinetics and fate of fusion

Controlled vesicle fusion has major advantages in diagnostic and drug delivery applications. We have designed a DNA hybridisation-based assay for directed fusion of vesicles upon mixing, and applied it in a recently published diagnostic assay to detect microRNA. In this proposal we propose static and stopped flow SANS experiments with contrast matching to study this DNA-mediated vesicle fusion mechanism and gain insight into 1) changes to vesicle shape in real time during fusion, and 2) mixing of the inner and outer membrane leaflets. We will confirm if DNA-functionalised liposomes proceed to hemi- or fully fused states, and if fusion can be controlled by modifying vesicle lipid composition and DNA concentration. The findings are essential to understand these vesicles fusion behaviour and can be directly applied to developing drug delivery vectors and diagnostic assays within our lab.