Micro/Nanobubble aided Non

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4. Micro/Nanobubble aided Non-viral delivery of

RNA

Professor SD Evans

Microbubbles (MBs) formed via microfluidics offer a facile way to produce

RNA based delivery vehicles for the targeted triggered delivery into cells.

Using ultrasound pulses to increase the MB oscillation amplitude (and /or burst the MBs) at the target site leading to temporary pore formation

(sonoporation) and enhanced uptake. We have shown that we can formulate the surface of the MB to carry charge (positive or negative) and that this can be used to load the MBs with oppositely charged polymers. [1]

Borden et al. in the USA have demonstrated that DNA / RNA can be loaded onto the MB surface and used as an effective delivery agent. [2]

Figure Left (c): MB+ polymer layers (of which one can be replaced by RNA; Left

(D) as per (C) with PEG layer. Right (E) as per (D) plus targeting agents.

We would propose to extend this work to the microbubbles and Nanobubbles produced in Leeds and would seek to establish with AZ i) efficacy of delivery / uptake of RNA for shedding ii) optimal loading efficiency iii) addition of targeting layers (adhiron, aperture, peptide,..) iv) multiple RNA layers

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