Arcturus Therapeutics, Inc.

Nitto-denko Corporation

Sanford-burnham Medical Research Institute

Capstan Therapeutics, Inc.

Priya Prakash Karmali

Joseph E Payne

Padmanabh Chivukula

Victor Knopov

Richard P Witte

Yanjie Bao

Violetta Akopian

Mohammad Ahmadian

John Gaudette

Zheng Hou

Kiyoshi Tachikawa

Steven Paul Tanis

Yoshiro Niitsu

Yasunobu Tanaka

Loren A Perelman

Sridhar C Nagarajan

Daiki Matsuda

Wenbin Ying

Jared Henry Davis

Sean Michael Sullivan

Amit Sagi

Jun Zhang

Lei Yu

David Webb

Robin Lee

Neda Safarzadeh

Jerel Boyd Lee Vega

Erkki I Ruoslahti

Elena Feinstein

Igor Mett

Hagar Kalinski

Kenjiro Minomi

Pattraranee Limphong

Michael Figa

Sharon Avkin-Nahum

Yun Liu

Christine Esau

Kumar Rajappan

Carlos G Perez-garcia

Venkata Ramana Kotamraju

Scott A Roberts

Andreas Wagner

Rajesh Mukthavaram

Jerel Vega

Samantha Murphy

Brenda Clemente

Marciano Rodriguez Sablad

Suezanne E Parker

John A Gaudette

Padmanabh Chivikula

C Nagarajan Sridhar

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

Disclosed are compositions of lipid nanoparticles (LNP) comprising an ionizable cationic lipid, a phospholipid, a sterol, and a PEG-lipid (non-functionalized and optionally functionalized). The functionalized PEG-lipid can be conjugated with a binding moiety to create a targeted LNP (tLNP). The disclosed tLNP preferentially deliver a nucleic acid molecule or other negatively charged payload to cells expressing a cell surface antigen recognized by the binding moiety of the tLNP, and are better tolerated, as compared to LNPs and tLNPs comprising ionizable cationic lipids found in marketed pharmaceuticals comprising LNPs.

Lipid nanoparticle formulations and compositions

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

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

Methods of preparing lyophilized lipid nanoparticle-nucleic acid compositions are provided. The methods comprise preparing a suspension of lipid nanoparticles with a monosaccharide and one or more excipients selected from thiosulfate, potassium sorbate, sodium benzoate, and iodixanol. Lyophilized lipid nanoparticle-nucleic acid compositions and methods of reconstituting and administering the same are further provided.

Method of lyophilizing lipid 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

A method of producing lipid-encapsulated RNA nanoparticles includes flowing an aqueous solution comprising an RNA through a 1tube having a first inner diameter (ID); the RNA comprises from about 6,000 to about 13,000 nucleotides; flowing an ethanol solution comprising lipids through a 2tube having a second inner diameter (ID), at a flow rate of about 0.2 to about 1 times relative to the aqueous solution through the 1tube, the lipids comprise a cationic lipid; and mixing the ethanol solution with the aqueous solution; the first ID and second ID and flow rates through the 1tube and 2tube are selected to produce a shear force sufficiently low to preserve the integrity of the RNA; the mixing produces an output solution flowing in the 1tube comprising a turbulent flow of the RNA and the lipids in between about ethanol, the lipid-encapsulated RNA nanoparticles having a bilayer structure.

Lipid nanoparticles encapsulation of large RNA

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.

The description is directed to ionizable lipids useful for enhancing the delivery of therapeutic agents in liposomes.

Lipids for therapeutic agent delivery formulations

Here described is a composition comprising a compound of formula I: wherein Rand Ris independently selected from a group consisting of Cto Calkyl, Cto Calkenyl, and oleoyl group; Rand Rare independently selected from a group consisting of Cto Calkyl, and Cto Calkanol; X is selected from a group consisting of &#x2014;CH&#x2014;, &#x2014;S&#x2014;, and &#x2014;O&#x2014; or absent; Y is selected from &#x2014;(CH), &#x2014;S(CH), &#x2014;O(CH)&#x2014;, thiophene, &#x2014;SO(CH)&#x2014;, and ester; n=1-4; a=1-4; b=1-4; c=1-4; and Zis a counterion.

Cationic lipids for therapeutic agent delivery formulations

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San Diego, CA, United States of America

Priya Prakash Karmali