Messenger RNA: Delivery Challenges and First Steps Towards a Novel Modality

Departmental Seminar
Michael Smith
Director of Process Development at Moderna
Host: Professor Valerie Pierre 

Abstract

Messenger RNA: Delivery Challenges and First Steps Towards a Novel Modality

The combination of messenger RNA and lipid nanoparticles (mRNA LNPs) represent a novel therapeutic modality with a range of potential applications. However, mRNA is challenged by unavoidably large molecular size, instability, and immunogenicity. Preclinical efforts have shown the utility of LNPs for efficient mRNA encapsulation and tissue-specific delivery. Through advancement in mRNA and lipid chemistry, together with progression in nanoparticle formulation and process science, many barriers were overcome towards robust protein expression in vivo. In addition, more recent evidence has emerged suggesting the ability to encapsulate multiple mRNA cargo within LNPs, enabling the expression and assembly of multi-subunit proteins. The totality of clinical outcomes exemplify progress in the past few years, driving enthusiasm for RNA therapeutics and the area of nanoparticle-mediated oligonucleotide delivery. 

Press References:

• https://www.instagram.com/tv/CJRLNzgrLx4/
• https://nymag.com/intelligencer/2020/12/moderna-covid-19-vaccine-program.html

Michael Smith

Michael “Mike” Smith currently serves as Director of Process Development at Moderna. In his role, Mike leads a cross-disciplinary science and engineering team developing lipid nanoparticle (LNP) formulation platforms for messenger RNA (mRNA). Mike is a self-proclaimed “nanoparticle geek” and has a deep curiosity for the physical chemistry of nanoparticle self-assembly. Leveraging the science of nanoparticle synthesis, the team has built robust scale-up capabilities that service Moderna’s ambitious development portfolio, which includes over 23 drug candidates in active development. More recently, Mike’s team was a major contributor towards the development of Moderna vaccine against SARS-COVID-2 (mRNA-1273). His efforts, together with the Moderna team, were featured in a recent CNN Hero’s segment and further showcased in NY Magazine (see links below).

Mike has led numerous scientific and engineering projects over seven years at Moderna. In years prior, Mike contributed to nanoparticle formulation efforts at Merck that include siRNA LNP and liposomal formulations. Prior to his time in industry, Mike received his PhD from Georgia Tech with a dissertation on the topic of stimuli-responsive hydrogel nanoparticles for therapeutic delivery.