Ultrasound-Assisted Delivery of mRNA

Based on the progress of physical technology and nanotechnology, a series of physical gene delivery methods have been developed. These physical methods have received increasing attention, due to their advantages of briefness and nontoxicity. In addition to electroporation, microbubble-assisted sonoporation, another transfection technique that exploits membrane pores, has been successfully utilized with mRNA vectors. Creative Biogene is a forward-looking research institute as well as an experienced supplier in biotech markets. Over the years, we have focused on the area of IVT mRNA delivery and explored several improved transfection techniques to deliver mRNA into cells. With state-of-the-art equipment and skillful experts, we are proud to offer an IVT mRNA delivery service using microbubble-assisted sonoporation for worldwide clients.

Fig1. Six proposed mechanisms for pore formation in the plasma membrane induced by sonoporation. (Delalande, A., et al., 2017)

What is sonoporation?

Sonoporation is to perforate the cell membrane by using ultrasound waves. The first use of ultrasound to transfect mammalian cells in vitro was in 1996. Because ultrasound can access deep tissues in a non-invasive way as well as allow remote manipulation at the single-cell level. The method has gained great interest and is now widely used for nucleic acid delivery.

Based on the combination of low-frequency ultrasound and gas-filled microbubbles (MBs), sonoporation is able to promote the delivery of molecules, including nucleic acids in the insonified tissue. Similar to electroporation, the ultrasound field can form membrane pores. There are two types of physical effects (including thermal and non-thermal effects) generated during ultrasound acts on the cell membrane. In the low-intensity ultrasound field, the non-thermal effects in terms of cavitation, radiation forces, and mechanical streaming are generated, which can be employed to perform ultrasound-mediated delivery. To improve the transfection efficiency of sonoporation, MBs are employed to combine with ultrasound. The engineering of MBs is critical for protection against nuclease degradation as well as a warranty of high nucleic acid concentration within the target tissue. The MBs should meet these requirements, such as being stable enough to withstand nucleic acids interaction, having a good size distribution for in vivo administration, as well as possessing acoustic activity to be detected by echography.

Fig2. Schematic representation of cationic microbubble(A) and the most used cationic agents(B). (Delalande, A., et al., 2017)

Physical transfection approaches, comparison between electroporation and sonoporation

Custom mRNA delivery service using microbubble-assisted sonoporation

The combination of ultrasound and gas-filled microbubbles (MBs) assisted delivery offers an attractive method for non-invasive targeted nucleic acid delivery. It is widely believed that the transfection efficiency of sonoporation is highly connected with the formulation of MBs and the targeted cell/tissue. According to our customers' specific projects, we can offer the best transfection strategy with a series of optimized parameters including the formulation of MBs, the acoustic parameters, nucleic acid/MB ratio and among others. Our service has been demonstrated to precisely introduce biologically active molecules into cells, allowing the visualization and genome editing of the target cells. In addition, our service can allow other available nanocarriers, such as polymeric nanoparticles, polymeric micelles, and liposomes, to be combined with sonoporation to enhance the transfection efficiency.

With years of professional and abundant experience, Creative Biogene is dedicated to offering customized mRNA delivery services to meet a wide range of clients' requirements. If you have any questions about our service, please don't hesitate to contact us. We look forward to providing services for your next project.