Arcturus Therapeutics, Inc.

Ultragenyx Pharmaceutical Inc.

Arcturus, Inc.

Padmanabh Chivukula

Joseph E Payne

Kiyoshi Tachikawa

Priya Prakash Karmali

Steven Paul Tanis

Yanjie Bao

Daiki Matsuda

Pattraranee Limphong

Sean Michael Sullivan

Jared Henry Davis

Carlos Gustavo Perez-Garcia

Amit Sagi

Christine Esau

Arisa Cale

David Webb

Sean Christopher Daugherty

Carlos G Perez-garcia

Jerel Boyd Lee Vega

Michael Figa

Kumar Rajappan

Luigi Warren

Christian W Cobaugh

Rajesh Mukthavaram

Suezanne E Parker

Angel I-Jou Leu

Jared Davis

Scott A Roberts

Hari Bhaskaran

Andreas Wagner

Jerel Vega

Samantha Murphy

Rachel Wilkie-Grantham

Marciano Rodriguez Sablad

Priya Karmali

Steven P Tanis

What is described is a compound of formula (1) wherein

Ionizable cationic lipid for RNA delivery

The present disclosure provides a modified human OTC protein having improved properties for the treatment of OTC deficiency in a patient. Preferably, the protein of the disclosure is produced from a codon optimized mRNA suitable for administration to a patient suffering from OTC deficiency wherein upon administration of the mRNA to the patient, the protein of the disclosure is expressed in the patient in therapeutically effective amounts to treat OTC deficiency. The present disclosure also provides codon optimized mRNA sequences encoding wild type human OTC comprising a 5' UTR derived from a gene expressed byfor use in treating OTC deficiency in a patient.

Compositions and methods for treating ornithine transcarbamylase deficiency

Provided herein are nucleic acid molecules encoding viral replication proteins and antigenic proteins or fragments thereof. Also provided herein are compositions that include nucleic acid molecules encoding viral replication and antigenic proteins, and lipids. Nucleic acid molecules provided herein are useful for inducing immune responses.

Compositions and methods for inducing immune responses

The present disclosure describes compositions and methods for treating ornithine transcarbamylase (OTC) deficiency. The compositions include a lipid formulation and messenger RNA (mRNA) encoding an OTC enzyme. The lipid formulations can comprise an ionizable cationic lipid in a lipid nanoparticle encapsulating the mRNA.

Compositions and methods for the treatment of ornithine transcarbamylase deficiency

ASGP-R binding molecular conjugates are provided. The conjugates are useful to deliver therapeutically effective amounts of biologically active molecules to target cells and tissues of a subject. Compositions are also provided comprising the molecular conjugates.

Asialoglycoprotein Receptor mediated delivery of therapeutically active conjugates

What is described is a method of synthesis of the compound of formula 1A, or a salt thereof, wherein

Method of synthesis of an ionizable cationic lipid

Provided herein are nucleic acid molecules encoding viral replication proteins and antigenic coronavirus proteins or fragments thereof. Also provided herein are compositions that include nucleic acid molecules encoding viral replication and antigenic proteins, and lipids. Nucleic acid molecules provided herein are useful for inducing immune responses.

Coronavirus vaccine compositions and methods

A method of producing a lipid-encapsulated RNA nanoparticle, comprising the steps a) flowing an aqueous solution comprising an RNA through a 1tube having an inner diameter (ID) of between about 0.1″ and 0.132″; b) flowing an ethanol solution comprising lipids through a 2tube having an ID of between about 0.005″ and 0.02″ at one third the flow rate of the aqueous solution through the 1tube, wherein the lipids comprise a cationic lipid; and c) mixing the ethanol solution with the aqueous solution by flowing the ethanol solution and the aqueous solution into a mixing module consisting of the 2tube perpendicularly joined to the 1tube; wherein the mixing produces an output solution flowing in the 1tube comprising a turbulent flow of the RNA and the lipids in between about 10% to 75% ethanol v/v, and wherein the lipid-encapsulated RNA nanoparticles have a bilayer structure.

Method of making lipid-encapsulated RNA nanoparticles

Nucleic acid immunization is achieved by delivering a nucleic acid (NA), e.g., a mRNA or a DNA, encapsulated within a lipid-NA nanoparticle. The NA encodes an immunogenic compound of interest. The lipid-NA nanoparticle is effective for in vivo delivery of NA to a vertebrate cell, including upon administration to a subject. The lipid-NA nanoparticle are incorporated in pharmaceutical compositions for immunizing subjects against various diseases.

Lipid particles for nucleic acid delivery

Nucleotides encoding a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein are provided herein. Also describe are mRNA constructs that can be used to express CFTR protein in vitro or in vivo. The mRNA constructs can be formulated in a lipid formulation and administered via inhalation to treat cystic fibrosis.

Nucleic acids and methods of treatment for cystic fibrosis

This invention provides a range of translatable polynucleotide and oligomer molecules for expressing a human phenylalanine hydroxylase (PAH), or a fragment thereof having PAH activity. The polynucleotide and oligomer molecules are expressible to provide the human PAH or a fragment thereof having PAH activity. The molecules can be used as active agents to express an active polypeptide or protein in cells or subjects. The agents can be used in methods for ameliorating, preventing, delaying onset, or treating a disease or condition associated with phenylketonuria, decreased metabolism of phenylalanine, or increased levels of phenylalanine in a subject.

Compositions and methods for treating phenylketonuria

A range of therapeutic mRNA molecules expressible to provide a target polypeptide or protein. The RNA molecules can contain one or more 5-methoxyuridines and 5-methylcytidines. Further provided are DNA templates, which can be transcribed to provide a target mRNA, and can have altered nucleotides, such as reduced deoxyadenosines. Also provided are processes for making the therapeutic mRNA molecules. The RNA molecules can be translated in vitro or in vivo to provide an active polypeptide or protein. The RNA molecules can be included in a composition used for preventing, treating, or ameliorating at least one symptom of a disease or condition in a subject in need thereof.

Translatable molecules and synthesis thereof

A method of producing a lipid-encapsulated RNA nanoparticle, comprising the steps a) flowing an aqueous solution comprising an RNA through a 1tube having an inner diameter (ID) of between about 0.1&#x2033; and 0.132&#x2033;; b) flowing an ethanol solution comprising lipids through a 2tube having an ID of between about 0.005&#x2033; and 0.02&#x2033; at one third the flow rate of the aqueous solution through the 1tube, wherein the lipids comprise a cationic lipid; and c) mixing the ethanol solution with the aqueous solution by flowing the ethanol solution and the aqueous solution into a mixing module consisting of the 2tube perpendicularly joined to the 1tube; wherein the mixing produces an output solution flowing in the 1tube comprising a turbulent flow of the RNA and the lipids in between about 10% to 75% ethanol v/v, and wherein the lipid-encapsulated RNA nanoparticles have a bilayer structure.

Growing community of inventors

San Diego, CA, United States of America

Padmanabh Chivukula