Exploiting Non-Linear Acoustics for Enhanced Molecular Delivery

Lead Research Organisation: University of Dundee
Department Name: Electronic Engineering and Physics


RNAi is a new form of therapy that allows faulty genes to be switched off in a wide range of genetic diseases and in cancer. The barrier to applying this revolutionary new form of medicine is how to deliver it into the body, since the molecules involved are larger than normal drugs and so cells require some help in taking this material up so it can have its beneficial effect. The main aim of this project is to revolutionise the delivery of these new therapeutics into the skin, as a test organ system by exploiting the penetrating effect of ultrasound activated microbubbles. Skin has the advantage of being on the outside of the body for easy access, and excess human skin from cosmetic surgery (breast reductions and tummy tucks) is readily available for experimentation to optimise delivery of RNAi molecules. In pursuit of this, we will develop an innovative new tool combining chemistry, ultrasound and arrays of microscopic painless needles for fast, effective and reliable delivery into skin at high coverage rates. Once optimised for skin diseases, this hand-held device will be readily adapted for use on internal organs using keyhole surgery methods, so that the potential applications of this device across all branches of medicine are huge. The team assembled in Dundee brings together a leading molecular biologist with a physicist, but supported by further international collaborators with diverse skills across many different fields, in order to piece together elements of technology in ways that have never been done before. The estimated market for solving the therapy delivery problem being tackled here is in the order of 10s of billions of dollars per year.
Ultrasound, as prescribed in the manner presented, looks like a very promising route to achieving that goal.

Technical Summary

RNA-interference (RNAi) has revolutionised biomedical sciences as a research tool and has enormous potential for treatment a host of genetic diseases and cancer. In 2004, the projected market for this new class of therapeutics was estimated at $25 billion in the USA alone. The major limiting factor preventing RNAi technology from clinical application is effective delivery. The skin is an attractive target organ for delivery development due its accessibility but the stratum corneum, the impermeable barrier layer at the epidermal surface, is difficult to cross. Here we have assembled a multidisciplinary team consisting of a molecular biologist with expertise in genetic skin disease and an physicist highly active in design of microfabrication of new medical devices for ultrasonic delivery of molecules (sonoporation), all based in a new translational research division within the 5* research environment at the University of Dundee. The team is supported by collaborators that include a clinical dermatologist, the CEO of a siRNA biopharma start-up and the leading experts in use of sonoporation for skin delivery and in use of microneedles for trans-stratum corneum delivery. The overarching objective for this project is to revolutionise the delivery of molecular therapeutics across the stratum corneum and into the underlying living tissue. This will be achieved by marrying the latest cutting edge findings drawn from ultrasound driven micro-fluid mechanics, with state-of-the-art RNAi biotechnology. Here, we make a quantum leap in procedures by coupling the initial penetrative passage through the stratum corneum with an active mode of subsequent dispersal into the viable dermis using ultrasound activated microbubbles that contain the siRNA. Delivery testing will involve use of human skin biopsy material. This scientific method, and the hardware developed in support of it are unique, and have not been attempted before.


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