Making Light Deliver: translation of methods of photoporation

The cell membrane represents the outer extremity of all cells. In mammals, this is a thin bi-layer film of lipids, embedded with various protein molecules at interspersed locations. The membrane encloses the cell, defines its boundaries and maintains the essential physico-chemical differences between the cytoplasm and the extracellular environment. Under normal circumstances, the lipid nature of the cell membrane acts as an impermeable barrier to the passage of most water-soluble molecules. Thus, the selective introduction of therapeutic agents to the inside of dysfunctional or diseased cells remains a key challenge. The St Andrews-Dundee team's original Basic Technology grant was aimed at developing two inter-related strands of research that would enable targeted drug delivery to cells and tissue at will. The studies have resulted in excellent research and papers and the methods of using tightly focused laser beams to create minute transient pores that permit therapeutic agents to be introduced has been the most promising. This technique, termed photoporation, offers a powerful method for single cell targeted transfection in a sterile fashion. In this next proposal we aim to translate our results and the developed technology into devices that will be common place in both universities and industry. This will be because these optical devices will be able to deliver biologically important material, ranging from genes through to prototype drugs, into a host of different biological systems such as its involvement in stem cell research, plant cells, agriculture through to in vivo mammalian tissue.

This Basic Technology translation grant will have a major impact. The team of Principal Investigators and postdoctoral researchers involved in this grant will benefit directly from the translation of the original basic technology, with an increase in their understanding at both a scientific/engineering level, but also through the interactions with industry and other researchers. The advance level of the research being performed, and exposure to best-practice science, will also impact on the postdoctoral team as they will emerge as specialists with highly sought after skills. The direct ongoing involvement of the core team (see track record) with charities and research councils will ensure that these organisations remain well appraised of the state of the art techniques that are being developed, which in turn will influence their future funding strategy and policies. There will also be the impact for the identified end-users who range from a wide range of research areas in Academia, Research Institutes and Societies and also Industry. Examples include: Biology: particularly Cell (including stem and plant cells) biology, Genetics, & Developmental biology - all of whom have expressed and interest in using our novel transfection technology under specific and well controlled circumstances. Chemistry: particularly Drug Development & Drug Delivery specialists who may wish to ascertain the effectiveness of small molecules as therapeutic agents in a controlled and quantitative manner. Physics: Researchers in photoporation and the fundamental processes underlying this technique (eg low electron plasma generation) will be interested in our data. Laser and optical engineers will be interested from the viewpoint of advanced instrumentation (laser development) and optical systems design including microfluidic environments. Medical: Surgeons/dermatologists broadly interested in laser based techniques, specifically photoporation for drug/gene therapies. Industry: As indicated in the proposal, the potential impact for the Biophotonics Instrumentation industry is significant. This could lead to future engagements with specific industries for drug development and drug discovery. Public Heath: The project focuses on an ability to transfect cells with potential therapeutic agents in both in-vitro and in-vivo contexts. This would in the longer term impact on our understanding of disease and its treatment. This could represent a significant impact to public health/ improved quality of life. Other benefits will come from the studies performed on Plant sciences as this impacts on Agriculture. Public Outreach/Understanding of Science: All of the core team have high profile outreach activities (eg the team has held PPE awards) ranging from school visits, through to open-days, public lectures, Science festivals, media events for dissemination. This attracts young people towards science careers and will also keep the public informed on the new directions in targeted drug delivery and the need for our studies.