Modernatx, Inc.

Other

Moderna Therapeutics, Inc.

Fundacion Para La Investigacion Medica Aplicada

Stephen G Hoge

Kerry Benenato

Vladimir Presnyak

Ellalahewage Sathyajith Kumarasinghe

Iain McFadyen

Joshua P Frederick

Ailin Bai

Susannah Hewitt

Staci Sabnis

Paolo Martini

Tirtha Chakraborty

Gilles Besin

William Joseph Issa

Edward John Miracco

Jennifer Nelson

Lin Tung Guey

Noubar Boghos Afeyan

Stephane Bancel

Gabor Butora

Atanu Roy

Antonin De Fougerolles

Amy E Rabideau

Joseph Senn

Matthew G Stanton

Sayda Mahgoub Elbashir

Giuseppe Ciaramella

Eric Yi-Chun Huang

Jeff Lynn Ellsworth

Justin Guild

Kristy M Wood

Joseph Beene Bolen

Ruchi Jain

Ding An

Xuling Zhu

Athanasios Dousis

Zhinan Xia

John Reynders

Jingsong Cao

Barry Ticho

Seymour De Picciotto

Nadege Briancon-Eris

Örn Almarsson

Matthias John

John Podobinski

Pedro Berraondo Lopez

Joseph Schariter

Divakar Ramakrishnan

Melissa J Moore

Antonio Fontanellas Roma

Michael H Smith

Charles Bowerman

Ben Geldhof

Allen Horhota

Jessica Cheney

Christopher Karl Mclaughlin

Matias Antonio Avila Zaragoza

Lei Jiang

Jeffrey Hrkach

Yan Xia

Ciarán Lawlor

David D Hile

Noubar B Afeyan

Iain Mcfadyen

Lain Mcfadyen

William Issa

John Van Wicheren Iii Reynders

The invention relates to mRNA therapy for the treatment of Acute Intermittent Porphyria (AIP). mRNAs for use in the invention, when administered in vivo, encode human porphobilinogen deaminase (PBGD), isoforms thereof, functional fragments thereof, and fusion proteins comprising PBGD. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to affect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of PBGD expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient PBGD activity in subjects, namely porphobilinogen and aminolevulinate (PBG and ALA).

Polynucleotides encoding porphobilinogen deaminase for the treatment of acute intermittent porphyria

The invention relates to mRNA therapy for the treatment of galactosemia type 1 (Gal-1). mRNAs for use in the invention, when administered in vivo, encode human galactose-1-phosphate uridylyltransferase (GALT), isoforms thereof, functional fragments thereof, and fusion proteins comprising GALT. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of GALT expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient GALT activity in subjects, namely galactose-1-phosphate (Gal-1-P).

Polynucleotides encoding galactose-1-phosphate uridylyltransferase for the treatment of galactosemia type 1

The invention relates to improved RNA compositions for use in therapeutic applications. The RNA compositions are particularly suited for use in human therapeutic application (e.g., in RNA therapeutics). The RNA compositions are made by improved processes, in particular, improved in vitro-transcription (IVT) processes. The invention also relates to methods for producing and purifying RNA (e.g, therapeutic RNAs), as well as methods for using the RNA compositions and therapeutic applications thereof.

High purity RNA compositions and methods for preparation thereof

The disclosure features methods of reducing or inhibiting an anti-drug antibody response in a subject, as well as methods of reducing or inhibiting unwanted immune cell activation in a subject to be treated with a messenger RNA (mRNA), comprising administering to the subject a mRNA, e.g., a chemically modified messenger RNA (mmRNA), encoding a polypeptide of interest, wherein the mRNA comprises at least one microRNA (miR) binding site for a miR expressed in immune cells, such as miR-126 binding site and/or miR-142 binding site, such that an anti-drug antibody response to the polypeptide or interest, or unwanted immune cell activation (e.g., B cell activation, cytokine secretion), is reduced or inhibited in the subject. The disclosure further provides therapeutic treatment regimens designed to reduce or inhibit ADA or unwanted immune cell activation (e.g., B cell activation, cytokine secretion) in a subject being treated with mRNA-based therapeutics.

Methods for therapeutic administration of messenger ribonucleic acid drugs

The invention relates to mRNA therapy for the treatment of Citrullinemia Type 2 ('CTLN2'). mRNAs for use in the invention, when administered in vivo, encode human Citrin, isoforms thereof, functional fragments thereof, and fusion proteins comprising Citrin. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of Citrin expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of biomarkers associated with deficient Citrin activity in subjects, namely ammonia and/or triglycerides.

Polynucleotides encoding Citrin for the treatment of Citrullinemia type 2

The invention relates to improved RNA compositions for use in therapeutic applications. The RNA compositions are particularly suited for use in human therapeutic application (e.g., in RNA therapeutics). The RNA compositions are made by inproved processes, in particular, improved in vitro-transcription (IVT) processes. The invention also relates to methods for producing and purifying RNA (e.g, therapeutic RNAs), as well as methods for using the RNA compositions and therapeutic applications thereof.

The invention relates to mRNA therapy for the treatment of Alagille syndrome (ALGS), mRNAs for use in the invention, when administered in vivo, encode JAGGED 1 (JAG1), isoforms thereof functional fragments thereof, and fusion proteins comprising JAG1, mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of JAG1 expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient JAG1 activity in subjects.

Polynucleotides encoding JAGGED1 for the treatment of Alagille syndrome

The invention relates to mRNA therapy for the treatment of hyperlipidemia. mRNAs for use in the invention, when administered in vivo, encode human lipoprotein lipase (LPL), isoforms thereof, functional fragments thereof, and fusion proteins comprising LPL. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto, mRNA therapies of the invention increase and/or restore deficient levels of LPL expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of triglycerides associated with deficient LPL activity in subjects.

Polynucleotides encoding lipoprotein lipase for the treatment of hyperlipidemia

The invention relates to mRNA therapy for the treatment of fibrosis and/or cardiovascular disease. mRNAs for use in the invention, when administered in vivo, encode human relaxin, isoforms thereof, functional fragments thereof, and fusion proteins comprising relaxin. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of relaxin expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient relaxin activity in subjects.

Polynucleotides encoding relaxin

The present disclosure provides methods of producing lipid nanoparticle (LNP) formulations and the produced LNP formulations thereof. The present disclosure also provides therapeutic and diagnostic uses related to the produced LNP formulations.

Preparation of lipid nanoparticles and methods of administration thereof

The invention relates to compositions and methods for the manufacture and optimization of modified mRNA molecules via optimization of their terminal architecture.

Terminally modified RNA

The invention relates to mRNA therapy for the treatment of cystic fibrosis. mRNAs for use in the invention, when administered in vivo, encode cystic fibrosis transmembrane conductance regulator (CFTR), isoforms thereof, functional fragments thereof, and fusion proteins comprising CFTR. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of CFTR expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient CFTR activity in subjects.

Polynucleotides encoding cystic fibrosis transmembrane conductance regulator for the treatment of cystic fibrosis

This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering agents in vivo including nucleic acids and proteins.

RNA formulations

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of signal-sensor polynucleotides, primary transcripts and mmRNA molecules.

Signal-sensor polynucleotides for the alteration of cellular phenotypes

The present disclosure relates to the use of nucleic acid (e.g., mRNA) combination therapies for the treatment of cancer. The disclosure provides compositions, and methods for their preparation, manufacture, and therapeutic use, wherein those compositions comprise at least two polynucleotides (e.g., mRNAs) in combination wherein the at least two polynucleotides are selected from the group consisting of (i) a polynucleotide encoding an immune response primer (e.g., IL23), (ii) a polynucleotide encoding an immune response co-stimulatory signal (e.g., OX40L), (iii) a polynucleotide encoding a checkpoint inhibitor (e.g., an anti CTLA-4 antibody), and, (iv) a combination thereof. The therapeutic methods disclosed herein comprise, e.g., the administration of a combination therapy disclosed herein for the treatment of cancer, e.g., by reducing the size of a tumor or inhibiting the growth of a tumor, in a subject in need thereof. In some aspects, the combination therapies disclosed herein disclosed are administered intratumorally.

mRNA combination therapy for the treatment of cancer

Growing community of inventors

Brookline, MA, United States of America

Stephen G Hoge