A Pilot Study of Microbubble-Delivered Gene Therapy Using High Intensity Focused Ultrasound (HIFU)

Oncolytic adenovirus is a frequently used viral vector for gene therapy in cancer treatments. However, they are highly susceptible to liver-drainage or rejection by the immune system upon injection. This leads to an inadequate gene-delivery to the target tumor or unnecessary delivery to healthy tissues, causing necrosis in different organs. This not only decreases the effectiveness of the therapy but also creates additional damages that may lead to severe side effects, outweighing the benefit of the treatment. In order to efficiently deliver the viral vector to the target tumor and tumor tissue only, the adenovirus is inserted into microbubbles. Microbubbles have been used to locally, temporally and reversibly open the blood-brain-barrier (BBB) under the influence of high intensity-focused ultrasound (HIFU). This increases the amount of gene delivered, decreasing the dose needed to successfully induce cell apoptosis in tumor cells. Understanding that HIFU induces the opening of BBB and degradation of microbubbles at proximate sites of the target tissue, it is still unknown whether the adenovirus can efficiently and effectively be delivered to cause successful apoptosis in local tumor cells. Our study investigates the possibility of minimally-invasive gene delivery using microbubbles with MRI-guided HIFU and confirms that the adenovirus can successfully be delivered into target tumor tissues.