Rapid onset of effect with mRNA therapeutics is demonstrated in the acute setting, imparting hepatic enzymatic activity with repeat dosing in small and large animals.
Non-human primate and rodent studies demonstrate tissue-targeted mRNA translation and mitigation of potential off-target effects through the use of microRNA binding sites.
Animal studies demonstrate that a challenging viral antigen, such as a multimeric, membrane-bound protein complex, encoded by mRNA, can elicit a robust, protective immune response.
Two clinical studies demonstrate that an LNP-formulated, modified mRNA vaccine can elicit a protective immune response with an acceptable safety profile.
| Title | Journal | Description | |
|---|---|---|---|
 |
Multi-antigenic, pentamer-based, human cytomegalovirus mRNA vaccines that elicit potent humoral and cell-mediated immunity | VaccineFebruary 2018 |
Animal studies demonstrate that a challenging viral antigen, such as a multimeric, membrane-bound protein complex, encoded by mRNA, can elicit a robust, protective immune response. |
 |
A modified mRNA-based Ebola vaccine elicits a robust immune response and protects guinea pigs from a lethal challenge | Journal of Infectious DiseaseDecember 2017 |
This preclinical study with a LNP-formulated, modified mRNA vaccine demonstrates 100% survival and higher protective antibody titers than previously observed with viral vector vaccines. |
 |
Induction of robust B cell responses after Influenza mRNA vaccination is accompanied by circulating hemagglutinin-specific ICOS+PD-1+CXCR3+ T follicular helper cells | Frontiers in ImmunologyNovember 2017 |
This non-human primate study of mRNA vaccines characterizes the cellular immune response that accompanies robust production of neutralizing antibodies, furthering our understanding of the immune signature associated with effective protection. |
 |
Rhesus macaque myeloid-derived suppressor cells demonstrate T cell inhibitory functions and are transiently increased after vaccination | Journal of ImmunologyNovember 2017 |
Results in non-human primates characterize the response of immune-suppressive cells to vaccination, expanding our understanding of the mechanisms underlying vaccine immunogenicity versus reactogenicity. |
 |
Efficient targeting and activation of antigen-presenting cells in vivo after modified mRNA vaccine administration in rhesus macaques | Molecular TherapyAugust 2017 |
This non-human primate study with mRNA vaccines characterizes the immune cells activated – and their subsequent priming of T cells – supporting our fundamental understanding of vaccine efficacy. |
 |
Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease | CellJuly 2017 |
This research demonstrates that LNP-formulated mRNA vaccines can induce protection against viral placental and fetal damage in mouse models, critical for vaccines against viruses that exhibit vertical transmission. |
 |
Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 Influenza viruses | Molecular TherapyApril 2017 |
Two clinical studies demonstrate that an LNP-formulated, modified mRNA vaccine can elicit a protective immune response with an acceptable safety profile. |
 |
Modified mRNA vaccines protect against Zika virus infection | CellFebruary 2017 |
This in vivo research demonstrates that a mRNA vaccine encoding components of a subviral particle can prevent disease. |
 |
Overview of vaccine adjuvants: introduction, history, and current status (Review) | Vaccine AdjuvantsOctober 2016 |
This review summarizes the current use and future prospects of adjuvants, which enhance the body's immune response to vaccines. |
| Title | Journal | Description | |
|---|---|---|---|
 |
An RNA toolbox for cancer immunotherapy | Nature ReviewsSeptember 2018 |
This review highlights the potential for RNA cancer immunotherapies, including mRNA applications in cancer vaccines and immune modulation. |
| Title | Journal | Description | |
|---|---|---|---|
 |
Biocompatible, Purified VEGF-A mRNA Improves Cardiac Function after Intracardiac Injection 1 Week Post-myocardial Infarction in Swine | Molecular Therapy Methods & Clinical DevelopmentApril 2018 |
Large animal studies demonstrate that direct injection of modified mRNA can produce local protein expression while maintaining immune silence, and can induce physiological effects at an organ level. |
 |
Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction | Nature BiotechnologySeptember 2013 |
This foundational paper establishes that direct injection of modified mRNA in mice can induce local physiological changes and could be an effective approach for regenerative therapeutics. |
| Title | Journal | Description | |
|---|---|---|---|
 |
Messenger RNA as an etiological treatment for acute intermittent porphyria | Nature MedicineOctober 2018 |
Rapid onset of effect with mRNA therapeutics is demonstrated in the acute setting, imparting hepatic enzymatic activity with repeat dosing in small and large animals. |
 |
Systemic messenger RNA therapy as a treatment for methylmalonic acidemia | Cell ReportsDecember 2017 |
Results in a mouse disease model suggest that repeat systemic administration of LNP-formulated mRNA can elicit intracellular protein expression in hepatocytes for rapid and sustained amelioration of disease. |
| Title | Journal | Description | |
|---|---|---|---|
 |
MicroRNAs Enable mRNA Therapeutics to Selectively Program Cancer Cells to Self-Destruct | Nucleic Acid TherapeuticsAugust 2018 |
Non-human primate and rodent studies demonstrate tissue-targeted mRNA translation and mitigation of potential off-target effects through the use of microRNA binding sites. |
 |
A Novel Amino Lipid Series for mRNA Delivery: Improved Endosomal Escape and Sustained Pharmacology and Safety in Non-human Primates | Molecular TherapyMarch 2018 |
Non-human primate and rodent studies demonstrate the potential for repeat dosing of mRNA safely and at therapeutically relevant levels with proprietary Moderna lipids. |
 |
Lipid nanoparticle packaging is an effective and non-toxic mRNA delivery platform in embryonic zebrafish | ZebrafishJanuary 2018 |
This study suggests that direct injection of LNP-formulated mRNA may be a valuable tool in the study of developmental biology given transfection of distinct tissues in a developing vertebrate embryo. |
 |
Safety evaluation of lipid nanoparticle-formulated modified mRNA in the Sprague-Dawley rat and cynomolgus monkey | Veterinary PathologyNovember 2017 |
In vivo studies with systemic delivery of modified mRNA in an industry standard LNP demonstrate therapeutic levels of protein expression and predictable pharmacology and toxicology. |
 |
Boosting intracellular delivery of lipid nanoparticle-encapsulated mRNA | Nano LettersAugust 2017 |
This research focuses on the mechanism of LNP endosomal escape, highlighting opportunities to increase LNP potency by improving the efficiency of escape. |
 |
Messenger RNA as a Novel Therapeutic Approach (Chapter) | RNA TherapeuticsMarch 2017 |
This chapter highlights recent advances in the delivery of nucleotide therapeutics and their application to mRNA therapeutics. |
 |
A sensitivity analysis of RNA folding nearest neighbor parameters identifies a subset of free energy parameters with the greatest impact on RNA secondary structure prediction | Nucleic Acids ResearchMarch 2017 |
This study explores the impact of folding energetics on mRNA secondary structure, contributing toward structure prediction and design of mRNA therapeutics. |
 |
N1-methyl-pseudouridine in mRNA enhances translation through eIF2α-dependent and independent mechanisms by increasing ribosome density | Nucleic Acids ResearchFebruary 2017 |
This paper explores the molecular mechanisms through which modified nucleosides can promote translation efficiency, which is critical to designing potent mRNA therapeutics. |
