Modernatx, Inc.

Moderna Therapeutics, Inc.

Vertex Pharmaceuticals, Inc.

Tirtha Chakraborty

Antonin De Fougerolles

Stephane Bancel

Atanu Roy

Sayda Mahgoub Elbashir

Susan Whoriskey

Matthias John

Jason P Schrum

Jeff Lynn Ellsworth

Justin Guild

Kenechi Ejebe

Kristy M Wood

Paul Hatala

Stephen G Hoge

Ron Weiss

Noubar Boghos Afeyan

Gilles Besin

Ruchi Jain

Eric Yi-Chun Huang

John Grant Aunins

Joshua P Frederick

Ante Sven Lundberg

William Joseph Issa

Chad Albert Cowan

Robert Carl Kauffman

Tony Ho

Ewelina Morawa

Michelle I-Ching Lin

Bibhu Prasad Mishra

Laura Sandler

Jerome Rossert

Brenda Eustace

Andrew Kernytsky

Todd Douglass Borland

Noubar B Afeyan

Elizabeth Jae-Eun Paik

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

Provided herein, in some embodiments, are methods and compositions for treatment of subjects with β-thalassemia and subjects with severe sickle cell disease using autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells.

CRISPR-CAS9 modified CD34+ human hematopoietic stem and progenitor cells and uses 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 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 invention relates to compositions and methods for the preparation, manufacture and therapeutic use of long-lived polynucleotides, primary transcripts and mmRNA molecules.

Long-lived polynucleotide molecules

Materials and methods for treating a patient with a hemoglobinopathy, both ex vivo and in vivo, and materials and methods for creating permanent changes to the genome that can result in at least one deletion, insertion, modulation, or inactivation of a transcriptional control sequence of a BCL11A gene in a cell by genome editing.

Materials and methods for treatment of hemoglobinopathies

Materials and methods for treating a patient with hemoglobinopathy, both ex vivo and in vivo and materials and methods for deleting at least a portion of a human beta globin locus on chromosome 11 in a human cell by genome editing and thereby increasing the production of fetal hemoglobin (HbF).

The present invention relates to compositions comprising and methods of using synthetic polynucleotides, e.g., modified mRNA, encoding CRISPR related proteins including dCAS9 and synthetic sgRNAs targeting a gene of interest.

Compositions comprising synthetic polynucleotides encoding CRISPR related proteins and synthetic sgRNAs and methods of use

Terminally Modified RNA

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 AD A or unwanted immune cell activation (e.g., B cell activation, cytokine secretion) in a subject being treated with mRNA-based therapeutics.

The invention relates to a pharmaceutical composition including a plurality of lipid nanoparticles having a mean particle size of between 80 nm and 160 nm and containing an mRNA encoding a polypeptide. The lipid nanoparticles include a cationic lipid, a neutral lipid, a cholesterol, and a PEG lipid. The mRNA contains a 5'-cap, 5&#x2032;-UTR, a 3&#x2032;-UTR, and a poly-A region with at least 100 nucleotides.

Modified Polynucleotides for the production of biologics and proteins associated with human disease

Described are methods for production of RNA transcripts using a non-amplified, linearized DNA template in an in vitro transcription reaction. Enzymatic 5' capping and oligo dT purification can also be included in the methods.

Manufacturing methods for production of RNA transcripts

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

Modified polynucleotides for the production of proteins

Growing community of inventors

Medford, MA, United States of America

Tirtha Chakraborty