University of Pennsylvania

The Johns Hopkins University

Vanderbilt University

Beth Israel Deaconess Medical Center, Inc.

Oxford University Innovation Limited

Triad National Security, LLC

Other

Boston Medical Center Corporation

George Mason Research Foundation, Inc.

Drew Weissman

Katalin Kariko

Jerome J Jendrisak

Gary A Dahl

Anthony Person

Judith Meis

Norbert Pardi

Dan H Barouch

James E Crowe, Jr

George M Shaw

Gary H Cohen

Harvey M Friedman

Tomas Hanke

Bette T M Korber

Stuart Campbell Ray

Michael Hogan

Andrew I Flyak

James Theiler

Sita Awasthi

Justin R Bailey

Mikell Paige

Katalin Karikó

Valerie Gouon-Evans

Michael Daro Buschmann

Manuel Carrasco

Mohamad Gabriel Alameh

Suman Alishetty

Earl Stoddard

Disclosed herein are methods of increasing the potency of nucleic acid loaded lipid nanoparticles (naLNPs) through certain novel and surprisingly superior LNP manufacturing techniques. Also disclosed are pharmaceutical compositions containing naLNPs manufactured according to the manufacturing methods described herein. The methods disclosed herein overcome major technical difficulties and high costs associated with previous LNP manufacturing techniques. The methods disclosed herein, therefore, greatly improve the industrial production of LNPs in unexpected ways thereby providing more potent naLNPs for nucleic acid delivery. Specifically, the invention disclosed herein are methods that show increased potency naLNPs due to increased mixing concentration of the lipids and mRNA during assembly.

Methods of lipid nanoparticle manufacture and compositions derived therefrom

The present application discloses compositions and methods for use of nucleoside modified mRNA that encode for at least one liver regenerative factor. The present invention also relates to compositions and methods for use of nucleoside modified mRNA complexed to nanoparticles. The disclosed compositions and methods are useful for treating acute liver diseases, chronic liver diseases, and/or acetaminophen (acetyl-para-aminophenol, APAP) overdose.

Nucleoside modified mRNA and uses thereof

Immunogenic compositions and methods of their use in eliciting immune responses to coronaviruses, such as SARS-CoV-2 are provided.

Conserved region T cell vaccines for coronavirus and methods of use

The present invention relates to compositions and methods for inducing an adaptive immune response against Hepatitis C virus (HCV) in a subject. In some embodiments, the present invention provides a composition comprising a nucleoside-modified nucleic acid molecule encoding a HCV antigen, adjuvant, or a combination thereof. For example, in some embodiments, the composition comprises a vaccine comprising a nucleoside-modified nucleic acid molecule encoding a HCV antigen, adjuvant, or a combination thereof.

Nucleoside-modified mRNA-lipid nanoparticle lineage vaccine for hepatitis C virus

The present invention relates to compositions and methods for inducing an adaptive immune response against Zika virus (ZIKV) in a subject. In certain embodiments, the present invention provides a composition comprising a nucleoside-modified nucleic acid molecule encoding a ZIKV antigen, adjuvant, or a combination thereof. For example, in certain embodiments, the composition comprises a vaccine comprising a nucleoside-modified nucleic acid molecule encoding a ZIKV antigen, adjuvant, or a combination thereof.

Compositions for inducing an immune response against zika virus

The present invention relates to compositions and methods for inducing an adaptive immune response in a subject. In certain embodiments, the present invention provides a composition comprising a nucleoside-modified nucleic acid molecule encoding an antigen, adjuvant, or a combination thereof. For example, in certain embodiments, the composition comprises a vaccine comprising a nucleoside-modified nucleic acid molecule encoding an antigen, adjuvant, or a combination thereof.

Nucleoside-modified RNA for inducing an adaptive immune response

This invention provides purified preparations of an RNA, oligoribonucleotide, or polyribonucleotide comprising a modified nucleoside, and methods of assessing purity of purified preparations of an RNA, oligoribonucleotide, or polyribonucleotide comprising a modified nucleoside.

Purification and purity assessment of RNA molecules synthesized with modified nucleosides

This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

RNA containing modified nucleosides and methods of use thereof

Compositions for the prevention and treatment of genital herpes, comprising nucleoside modified mRNAs that encode herpes simplex virus (HSV) glycoproteins, including those involved in virus entry and immune evasion, and methods of use thereof.

Modified MRNA vaccines encoding herpes simplex virus glycoproteins and uses thereof

The present invention provides compositions and methods for reprogramming somatic cells using purified RNA preparations comprising single-strand mRNA encoding an iPS cell induction factor. The purified RNA preparations are preferably substantially free of RNA contaminant molecules that: i) would activate an immune response in the somatic cells, ii) would decrease expression of the single-stranded mRNA in the somatic cells, and/or iii) active RNA sensors in the somatic cells. In certain embodiments, the purified RNA preparations are substantially free of partial mRNAs, double-stranded RNAs, un-capped RNA molecules, and/or single-stranded run-on mRNAs.

RNA preparations comprising purified modified RNA for reprogramming cells

Nucleoside-modified RNA for inducing an immune response against zika virus

The present invention provides compositions for the prevention and treatment of genital herpes, comprising nucleoside modified m RNAs that encode herpes simplex virus (HSV) glycoproteins, including those involved in virus entry and immune evasion, and methods of use thereof.

Modified mRNA vaccines encoding herpes simplex virus glycoproteins and uses thereof

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Wynnewood, PA, United States of America

Drew Weissman