Bacterial ‘OMV’ deliver siRNA straight to the target: A completely new way of delivering anti-cancer agents.
Scientists see RNA interference (RNAi) as a way to turn off a gene that has the potential to cause cancer. Despite this potential powerful tool, researchers studying the technique have been stymied by one major technological problem: How to deliver RNAi agents to target tissues?
A completely new way of delivering anti-cancer agent (siRNA) to tumours, using genetically engineered, bacterially derived outer membrane vesicles (“OMV”), has been tested for the first time in an animal model and was found to be safe, well-tolerated and therapeutically effective.
The research, which is published in the ACS publication ACS Nano (2014, 8 (2), pp 1525–1537) by the research group of Professor Sangyong Jon in the Department of Biological Sciences at KAIST, suggests that it could be possible to use this new OMV-based strategy to deliver siRNA directly to tumour cells, thereby reducing undesired side-effects.
The OMV’s are made from a genetically engineered, mutant bacteria with low endotoxic activity and which express Human epidermal growth factor receptor 2 (HER2) specific high affinity molecule ‘Affibody’ as targeting ligands. The OMV measures around 200 nm, and can be loaded with siRNA using a simple electroporation protocol. Such siRNA-packaged OMVs (AffiHER2OMVsiRNA) can home in on the target by engaging with tumour cell surface receptors (e.g. HER2). This means that the AffiHER2OMVsiRNA target the cancer cells, while avoiding normal cells devoid of the same receptors”, said Professor Jon. This research provides compelling evidence that AffiHER2OMVsiRNA could specifically deliver the packaged siRNA at therapeutically effective concentrations, as authors (V. Gujrati, et al.) reported the regression of tumor growth due to target gene silencing in a xenograft model in vivo. In this respect, the use of ‘AffiHER2OMVsiRNA’ is a novel and promising technique offering improved anti-tumour activity with reduction in adverse side-effects.
The bacterally-derived nano carriers help demonstrate a very interesting concept; previous efforts to develop targeted nanoparticles have focused on synthetic methods which are very expensive, limiting their clinical application. Most of the expense in drug development lies in the process of synthesis / manufacturing that relates to the ease or difficulty in production. This proposed technique bypasses this; large scale fermentation and purification tools may allow for high-speed, controlled production of OMVs on pilot scale. Additionally, the simple siRNA loading technique makes the system more efficient and cost effective. This current study provides a strategic nanomedicinal direction for the development of biological nanocarriers.
This research was supported by grants from the Bio & Medical Technology Development Program of the National Research Foundation (no. 2013035952) and by the Intelligent Synthetic Biology Center of Global Frontier Project funded by the Ministry of Science, ICT & Future Planning (no. 2013M3A6A8073557).
Related article: Vipul Gujrati et al. ACS Nano, 2014, 8 (2), pp 1525–1537.
Lab homepage: http://www.bionanolab.co.kr/