Versatile gene delivery targeting via Ultrasound and gas Microbubbles

ABSTRACT

The COVID-19 crisis and the rapid development of highly effective mRNA vaccines opened a new era for gene therapy. While viral vectors were for a long time the only tool for efficient delivery, new non-viral vectors have recently emerged, spawning new opportunities (indications, tissues, etc.). A new one is set to take off thanks to its safety profile, its specificity toward tissues, and its versatility toward both genetic materials and indications. Gas-filled microbubbles (MB), clinically used as ultrasound (US) contrast agents, have proven their benefits in various animal models and clinical applications for targeted delivery of drugs/genes. Herein, we disclose the development of new MB formulations allowing the delivery of various genetic materials at a specific location under the control of an ultrasound probe. We set forth a study to elicit the expression of a foreign enzyme in a liver mouse model. To this aim, MB were systemically co-injected with a Luciferase pDNA (6 to 65 mug) in the tail vein, then Ultrasound were delivered at MB arrival in the liver. The effective pDNA transfection was observed by bioluminescence 24 hours after treatment. Mice were divided into three groups pDNA alone;pDNA with US;pDNA with US and MBs (n >= 5). The use of our MB allowed increasing the signal up to 5 folds in comparison to the US alone. These results highlight the potential of MB plus US to efficiently deliver locally genetic material without any safety concerns.