Jana Schembera is a pharmacist by training and a PhD student in the group of Prof. Regina Scherließ at Kiel University. The aim of her doctoral thesis is the development of an inhalable dry powder platform for mRNA vaccines.

During her pharmacy studies she gained first insights in the pharmaceutical industry as an intern within the inhalation characterisation team in the Pharmaceutical Sciences Department of AstraZeneca in Gothenburg.

In 2018 she completed her studies of pharmacy at Kiel University and spent one half of her practical year at Boehringer Ingelheim in Biberach an der Riß. At Boehringer Ingelheim she joined a group handling late-stage drug product development to gain further industrial experience. After being registered as a pharmacist she came back to Kiel University in 2020 to start her PhD in the field of inhalation.

Apart from her research project she is responsible for the practical teaching of pharmaceutics to pharmacy students and continuing her training to become a specialised pharmacist in pharmaceutics and analytics.

Project summary

The route of administration has tremendous impact on the efficacy of pharmaceutical products such as vaccines. As many viral infections enter the body through the respiratory tract, the aim of my doctoral thesis is the development of an inhalable dry powder platform for mRNA vaccines. The delivery of vaccines to the respiratory tract aims directly at the main entry point of respiratory pathogens and the mucosal immune system.
Delivery of mRNA into eukaryotic cells requires the use of transfection reagents such as lipids forming lipoplexes with the mRNA. The lipid carrier not only enhances transfection efficiency but protects the mRNA against hydrolysis and RNases as well. To focus on the formulation in the solid state we chose two well-established lipids for lipoplex formulation in an equal weight ratio: the cationic lipid DOTAP and the neutral lipid DOPE.
In order to determine the most effective lipoplex composition, I investigated the efficiency of transfecting Calu-3 cells with various weight ratios of mRNA and the equal mixture of the two lipids. As a model system, I used reporter gene mRNA coding for firefly luciferase. A luminescence assay measures the abundance of this enzyme. This assay system also verifies that the mRNA is still intact and translatable to a functional protein.
After determining the best working weight ratio, I investigated the compatibility of excipients commonly used in inhalation with mRNA-lipoplexes during transfection and their particle characteristics. These excipients are going to form the matrix surrounding the mRNA-lipoplexes in inhalable particles. As my next steps, I am going to spray dry the mRNA-lipoplexes and excipients in a solution together to reach a particle size less than 5 µm. The spray drying process is a critical step because the formulation and process parameters have to ensure the integrity of mRNA and lipids to preserve a proper transfection efficiency.
One of the experts in the field of mRNA formulation for the respiratory tract is Jenny Lam, the DDL2020 Emerging Scientist Award Winner. Jenny Lam and her group were among the first reporting dry powder delivery of mRNA to the respiratory tract to induce transfection. Thus, I plan a scientific stay in her lab for two weeks to get a deeper insight and hands-on experience especially in the quantitative analysis of mRNA in complex matrices. Due to the expertise of Jenny Lam’s group utilising polymers as vesicles, I hope to find a way of adapting their methods to my lipid-vesicles and transferring them to Kiel. Apart from this, I aim to obtain new perspectives for the evaluation of my own procedures, to develop innovative methods, and to gain insights into in vivo assessment.
The overall aim of this project is the development of a readily adaptable dry powder platform for pulmonal mRNA vaccination. To fulfil this challenging task, expertise for tailored drug delivery and know-how in molecular biology need to be synergised.

Career Development Award Proposal

Early on in my studies, I discovered an interest in Pharmaceutics and started to work as a student assistant within the group of Prof. Regina Scherließ at Kiel University. A key aspect of the group’s research is the development and characterisation of inhalable formulations, especially dry powder formulations. During my time as a student assistant, I was able to gain an impression of the complexity and challenges of respiratory drug administration, as well as to grasp its tremendous potential. During an internship, I had the opportunity to gain insight in the work of the inhalation characterisation team in the Pharmaceutical Sciences Department of AstraZeneca in Gothenburg. Here I got to know the industrial point of view on formulations meant for inhalation and their aspects concerning pharmaceutical activity in pre-clinical development and at the start of clinical trials.
Subsequently, after finishing my studies I spent one half of my practical year at the main German research site of Boehringer Ingelheim in Biberach an der Riß where I joined a group handling late-stage drug product development. In this group, I worked on my own project within which I established a newly arrived instrument for particle size measurements in order to support the analytics of late-stage drug products. My time at Boehringer Ingelheim and AstraZeneca did not only give me a very valuable peek into the world of industrial research, but it also emphasised how many facets along the way critically influence the efficacy and quality of the finished formulation.
Now, I am a registered pharmacist and a doctoral candidate in the group of Prof. Regina Scherließ at Kiel University. During my past two years, I was not only doing research but also spending half of my time teaching students in the second and fourth year of their pharmacy studies. In the second year students learn about the common formulations, which have to be prepared in a public pharmacy, and the fourth year is all about formulations that are produced in industry. Watching the students enhance their independent thinking and scientific competences is one of the best parts of my teaching duties. Teaching future pharmacists comes with great responsibility. For example, some day in the pharmacy, they may need to prepare capsules meant for children. Apart from this I am currently introducing a master student into the world of cell culture and providing advice on experiment design.
Whenever I see the students develop their skills, I think about how I can develop myself further. This comprises enhancing my teaching skills and especially becoming a better researcher as well as making progress with my research project. I am convinced visiting a foreign lab and seeing their way to approach research questions and address challenges is going to benefit both my personal and research progress.
The goal of my research project is the development of an inhalable dry powder formulation for mRNA vaccination. Already at the beginning of my time as a doctoral candidate, I realised that the industrial insights are often not suitable for formulation development in academia.
Apart from this I am the first and currently only researcher working with mRNA in my department. Hence, I started from scratch and established handling procedures and analytics of mRNA in our lab. After facing many challenges working out the basics and gaining experience in performing complex assays, I began with the actual research and formulation development.
Now, with Covid-19 not interfering to such extends anymore, I would greatly benefit from visiting another academic lab that is highly experienced in handling mRNA.
This opportunity would allow me to learn innovative techniques and reflect as well as improve my own methods. It would also show me aspects I might have missed. In addition, this new point of view would give me the chance to enhance my creativity of implementing procedures, and my abilities of overcoming challenges and solving problems. As my stay will only last two weeks, I will also have to put my time management and team working skills to the test.
The visit would not only add to my scientific expertise, but it would also give me the chance of networking and getting in touch with scientists working in my field on an international level. I aim to stay in touch with the group and hopefully a joint project can be approached together in the future. This is an opportunity to be recognised by the international community, which will enhance the progress of my project and career.
As I love to travel and get to know people, I was happy to attend my first face-to-face conference, the PBP World Meeting in Rotterdam in March this year, where I presented a poster with the title “Transfection of Calu-3 cells with mRNA/DOTAP:DOPE-lipoplexes: influence of weight ratio and forming media”. After that experience, I am thrilled for my first face-to-face Drug Delivery to the Lungs conference in the end of this year and looking forward to presenting the next steps of my work.
Since the spirit of scientific exchange is something I never want to miss, I plan to proceed with formulation development for inhalation in either academia or the industry after finishing my doctoral thesis in 2024.
Succinctly, the experiences of the stay in Jenny Lam’s lab are going to enhance my chances of a confident scientific carrier, bring me a huge step closer to the inhalable dry powder platform for mRNA vaccines, and provide me with a data set I would like to publish in a manuscript and present at the DDL 2023.