Massachusetts Medical Society: Shattuck Lecture Series

Shattuck Lecture Series


132nd Annual Shattuck Lecture — Nucleoside Modified mRNA-LNP Therapeutics

Friday, May 20, 2022, 12:15 - 1:15 p.m.

**View the 2022 Annual Shattuck Lecture**


Lecturer

Drew Weissman, MD, PhD

Drew Weissman, MD, PhD
Roberts Family Professor in Vaccine Research, Perelman School of Medicine, University of Pennsylvania
To learn more about Dr. Drew Weissman, click here.


Moderator

Eric J. Rubin, MD, PhD

Eric J. Rubin, MD, PhD
Editor-in-Chief, The New England Journal of Medicine, NEJM Group
To learn more about Dr. Eric J. Rubin, click here.


Lecture Description

The Shattuck Lecture Series is sponsored by the MMS Committee on Publications and the New England Journal of Medicine. Dating back to 1890, this lecture is to be presented by “some suitable person or persons, of historical or other essays on the climate of said commonwealth, on the diseases of its inhabitants, and on such other subjects as the said society or its government may select.”

Vaccines prevent 4-5 million deaths a year, making them the principal tool of medical intervention worldwide. Nucleoside-modified mRNA was developed over 15 years ago and has become the darling of the COVID-19 pandemic with the first 2 FDA approved vaccines based on it. These vaccines show greater than 90% efficacy and outstanding safety in clinical use. The mechanism for the outstanding immune response induction is the prolonged production of antigen, leading to continuous loading of germinal centers and the adjuvant effect of the LNPs, which selectively stimulate T follicular helper cells that drive germinal center responses. Vaccine against many pathogens, including HIV, HCV, HSV2, CMV, universal influenza, coronavirus variants, pancoronavirus, Nipah, norovirus, malaria, TB, are currently in development. Nucleoside-modified mRNA is also being developed for therapeutic protein delivery. Clinical trials with mRNA encoded monoclonal antibodies are under way, and many other therapeutic or genetic deficient proteins are being developed. Finally, nucleoside-modified mRNA-LNPs are being developed and used for gene therapy. Cas9 knockout to treat transthyretin amyloidosis has shown success in phase 1 trials. We have developed the ability to target specific cells and organs, including lung, brain, heart, CD4+ cells, all T cells, and bone marrow stem cells, with LNPs allowing specific delivery of gene editing and insertion systems to treat diseases such as sickle cell anemia. Nucleoside-modified mRNA will have an enormous potential in the development of new medical therapies.

Learning Objectives

1. To describe the mechanisms that give mRNA-LNP vaccines potent neutralizing antibody responses

2. To explain the utility and potential uses of targeted LNP delivery of modified mRNA

3. To identify the potential mechanisms of toxicity of nucleoside-modified mRNA and lipid nanoparticles


Program Fees

This program is offered free of charge.





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