Exploiting Non-Linear Acoustics for Enhanced Molecular Delivery

RNAi是一种新的治疗形式，它允许在广泛的遗传疾病和癌症中关闭有缺陷的基因。应用这种革命性的新型药物的障碍是如何将其输送到体内，因为所涉及的分子比普通药物大，因此细胞需要一些帮助才能吸收这种物质，从而发挥其有益的作用。该项目的主要目的是通过利用超声波激活微泡的穿透作用，彻底改变这些新疗法进入皮肤的方式，作为测试器官系统。皮肤的优点是位于身体外部，易于接触，而且整容手术（乳房缩小和腹部整形）产生的多余人体皮肤很容易用于实验，以优化RNAi分子的递送。为了实现这一目标，我们将开发一种创新的新工具，结合化学，超声波和微型无痛针头阵列，以高覆盖率快速，有效和可靠地进入皮肤。一旦针对皮肤疾病进行了优化，这种手持设备将很容易适用于使用锁孔手术方法的内部器官，因此该设备在所有医学分支的潜在应用是巨大的。在邓迪组建的团队汇集了一位领先的分子生物学家和一位物理学家，但得到了来自许多不同领域的不同技能的国际合作者的进一步支持，以便以前所未有的方式将技术元素拼凑在一起。据估计，解决治疗递送问题的市场规模在每年数百亿美元左右。超声，按照所提出的方式，看起来是实现这一目标的一个非常有希望的途径。

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.