Development of lipid-based delivery systems for mRNA vaccines and therapeutics – The future is brighter

Mohamad-Gabriel Alameh, PhD
Postdoctoral fellow
Infectious Disease Division
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA, USA

This conference is part of the the IRCM Early-Career Scientist Seminar Series (ECS³), a groundbreaking initiative whose mission is to showcase early career scientists. This is a great opportunity to discover the exciting projects of these researchers in training in front of a multidisciplinary audience.

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In person: 

IRCM Auditorium
110, avenue des Pins O, H2W 1R7 Montreal
Wearing a mask is mandatory at all times

Online:

Zoom Link : https://zoom.us/j/95269762104
ID : 952 6976 2104
Code : 476372

IRCM conferences are set to occur under a hybrid format. However, please note that last-minute changes to online-only lectures may occur due to unforeseen circumstances. We invite you to visit this webpage again a few days before attending.

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About the conference:

mRNA based vaccines were rapidly deployed and played a major role in curbing the COVID-19 pandemic. I will give an overview of the technology, including small and large scale manufacturing of nucleoside modified mRNA, encapsulation into lipid nanoparticles (LNPs), and discuss the critical parameters that influence potency, reactogenicity, and immunogenicity of the platform. l will present data demonstrating that LNPs are broadly applicable adjuvants that induce strong Tfh responses (published in Immunity), discuss the preclinical development of a PanCoV mRNA vaccine (Part of a CEPI grant) and a C. difficile vaccine (BioNTech sponsored), and provide an quick overview of our experience building the mRNA-LNP platform in low and middle income countries and show data from a phase I/II trial in Thailand (Ongoing). I will summarize current projects including the development of a proprietary library of lipids, determination of structure-activity relationships, and strategies to use computational models for the discovery and development of improved formulations.

About Mohamad-Gabriel Alameh :

Dr. Mohamad-Gabriel Alameh holds a PhD in Biomedical Engineering from Polytechnique Montréal and currently pursues postdoctoral training in the Perelman School of Medicine of the University of Pennsylvania, under the mentorship of Dr. Drew Weissman. His work focuses on the development of second-generation mRNA vaccines and novel adjuvants, as well as on the elaboration of automated production and purification processes for in vitro-transcribed mRNA. Dr. Alameh is the scientific co-founder and the Head of platform at AexeRNA Therapeutics, as well as the co-director of the Engineered mRNA and Targeted Nanomedicine Core at the University of Pennsylvania. His key contributions to grant applications have helped secure significant funding for his team, from prestigious CIHR and NSERC programs. With six approved or provisional patents, close to 30 book chapters and articles published in high-impact journals such as Immunity and Cell Host & Microbe, or in various stages of preparation, and over 800 citations, Dr. Alameh is on track towards a productive and impressive career as a researcher.

Please tell us about your career path, leading up to your application to the ECS³ program

I received my B.S. and M.S. degrees from the University of Montreal, and my Ph.D. in Biomedical Engineering from Polytechnique Montreal under the supervision of Prof. Michael D. Buschmann. My thesis work focused on understanding the intrinsic and extrinsic parameters affecting chitosan-siRNA nanoparticle macromolecular properties and their effect on in vitro, and in vivo efficacy; a work that has led to better understanding of chitosan-nucleic acid design principles. During the final years of my Ph.D. I led the Biology subdivision of the Biomaterial and Cartilage laboratory at Polytechnique Montreal.

I joined the laboratory of Dr. Drew Weissman at the University of Pennsylvania as a Postdoctoral Fellow in 2018, where I lead multiple mRNA based vaccine projects (e.g. Clostridium difficile, PanCoV/PanSarbeco…) as well as projects to better understand the interaction of lipid nanoparticles with the immune system. My work has been published in prestigious journals such as Immunity (I.F. 31.74), and contributed to phase I/II clinical trials (Manuscript under review in NEJM).

I am also involved in the development of novel proprietary lipids, adjuvants and have a strong interest in mRNA construct and process optimization (e.g. in vitro transcription reactions, and process scale up). I cofounded AexeRNA therapeutics, a company that develops safe and potent lipid nanoparticles for nucleic acid based therapeutics. 

At Penn, I built and direct the University of Pennsylvania Engineered mRNA and Targeted Nanomedicine Core. My team automated and robotized the in vitro transcription process, and is now working on the automation of the purification process to streamline RNA production and supply RNA to multiple collaborators and companies across the globe.

Please tell us about your passion for research. What motivates you most about your work?

I view research as a mean to find solutions for problems that would allow us to improve our lives and/or our ecosystems/habitat. It is a way to progress at the individual and societal levels. What motivates me the most about my work it’s the translational aspect, and its current and potential impact on society.

Please tell us about the next steps of your career. How will participating in the ECS³ program help you progress as a researcher?

Developing my independent research programs and train the next generation of researchers. Alongside, I am also interested in establishing meaningful collaborations between industry and academia to mediate the advancement of research in my field. I am particularly interested in translational research, and the development of therapeutics. I would like in the short term to build the infrastructure, and the network, to be able in the mid-to long term to drive the bench-to bedside development of therapeutics. In addition, working on novel ideas to generate additional intellectual property is another aspiration of mine for both the short and long term.

ECS³ provides a platform to share my research with an interdisciplinary and clinical community at the IRCM. The ECS³ provides a networking platform allowing the IRCM scientific community to assess their interest in our work, exchange/expand ideas, and foster collaborations with seasoned researchers. The ECS³ provide additional visibility, vital in my current and future employment.

Please tell us about your professional goals. What do you hope to accomplish as a scientist?

Develop new technologies, including delivery systems with clinical application and evaluate their preclinical and clinical efficacy to ensure lab to market transition. As a scientist, my aim is to improve our understanding of lipid based nanoparticles, understand structure activity relationships, and elucidate the design principles for clinical translation. I aim to improve technologies, including cheaper technologies that will allow to decrease disparity and improve equity (e.g. mRNA vaccine) and to make the genetic medicine more accessible, especially for low income countries. I also aspire to contribute to the democratization of knowledge and minimizing knowledge gaps/misinformation.