Abstract: 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.

Abstract: Peptides and Peptide-lipid conjugates are provided in which the peptide has the general Formula (I) wherein, A1 is selected from serine, threonine, O—C1-6 alkyl serine, and O—C1-6 alkyl threonine; A2 is selected from serine, threonine, O—C1-6 alkyl serine, and O—C1-6 alkyl threonine; A3 is selected from glutamic acid, glutamine, asparagine, and aspartic acid; A4 is proline; each A5 is independently selected from a natural or modified amino acid; The peptide-lipid conjugates can be used in lipid formulations for the delivery of nucleic acids.

Abstract: A lipid composition containing a nucleic acid, wherein the lipid composition comprises a peptide-lipid conjugate, is provided. The peptide of the peptide-lipid conjugates can be from 4 to 52 amino acids in length. Methods of using the lipid composition in the in vivo delivery of nucleic acids are further provided.

Abstract: This invention provides a range of translatable polynucleotide and oligomer molecules for expressing a human amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL), or a fragment thereof having AGL activity. The polynucleotide and oligomer molecules are expressible to provide the human AGL or a fragment thereof having AGL 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 reduced activity of amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) in a subject.

Abstract: 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.

Abstract: This invention provides a range of translatable polynucleotide and oligomer molecules for expressing a human amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL), or a fragment thereof having AGL activity. The polynucleotide and oligomer molecules are expressible to provide the human AGL or a fragment thereof having AGL 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 reduced activity of amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) in a subject.

Abstract: The present disclosure provides a modified human protein having improved in vivo stability. The modified human protein has been altered from a wild-type human protein at either at least one ubiquitination site, at the signal peptide portion, or both. The protein of the disclosure can be produced from a codon optimized mRNA suitable for administration to a patient suffering from deficiency of the wild-type protein, wherein upon administration of the mRNA to the patient, the modified protein of the disclosure is expressed in the patient in therapeutically effective amounts.

Abstract: 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.

Abstract: Disclosed herein is a compound of Formula I, wherein R1 is a branched chain alkyl consisting of 10 to 31 carbons; R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons, or a branched chain alkyl consisting of 10 to 31 carbons; L1 and L2 are the same or different, each a linear alkane of 1 to 20 carbons or a linear alkene of 2 to 20 carbons; X1 is S or O; R3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt or solvate thereof.

Abstract: This invention provides expressible polynucleotides, which can express a target protein or polypeptide. Synthetic mRNA constructs for producing a protein or polypeptide can contain one or more 5? UTRs, where a 5? UTR may be expressed by a gene of a plant. In some embodiments, a 5? UTR may be expressed by a gene of a member of Arabidopsis genus. The synthetic mRNA constructs can be used as pharmaceutical agents for expressing a target protein or polypeptide in vivo.

Abstract: 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.

Abstract: 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.

Abstract: This disclosure encompasses compounds and compositions useful in methods for medical therapy, in general, for inhibiting expression of PDGFRB in a subject. The compounds have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers comprising UNA monomers and nucleic acid monomers.

Abstract: 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.

Abstract: What is described is a compound of formula I consisting of a compound in which R1 is a branched chain alkyl consisting of 10 to 31 carbons; R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons; L1 and L2 are the same or different, each a linear alkylene or alkenylene consisting of 2 to 20 carbons; X1 is S or O; R3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.

Abstract: This invention provides expressible polynucleotides, which can express a target protein or polypeptide. Synthetic mRNA constructs for producing a protein or polypeptide can contain one or more 5? UTRs, where a 5? UTR may be expressed by a gene of a plant. In some embodiments, a 5? UTR may be expressed by a gene of a member of Arabidopsis genus. The synthetic mRNA constructs can be used as pharmaceutical agents for expressing a target protein or polypeptide in vivo.

Abstract: What is described is a compound of formula I consisting of a compound in which R1 is a branched chain alkyl consisting of 10 to 31 carbons; R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons; L1 and L2 are the same or different, each a linear alkylene or alkenylene consisting of 2 to 20 carbons; X1 is S or O; R3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.

Abstract: What is described is a trinucleotide cap analog comprising m7G(5?)p3-N1pN2 for increased efficiency of in vitro transcription of m7G(5?)p3-RNA, wherein m7G is N7-methylguanosine or analog, (5?)p3 is a 5?,5?-triphosphate bridge, and N1 or N2 or both ribonucleotide analogs linked to each other by a phosphate, p, and wherein the trinucleotide cap analog increases the efficiency of in vitro transcription.

Abstract: Disclosed herein is a compound of Formula I, wherein R1 is a branched chain alkyl consisting of 10 to 31 carbons; R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons, or a branched chain alkyl consisting of 10 to 31 carbons; L1 and L2 are the same or different, each a linear alkane of 1 to 20 carbons or a linear alkene of 2 to 20 carbons; X1 is S or O; R3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt or solvate thereof.

Abstract: What is described is a compound of formula (1) wherein R1 and R2 are the same or different, each a linear or branched alkyl with 1-9 carbons, or an alkenyl or alkynyl with 2 to 11 carbon atoms; L1 and L2 are the same or different, each a linear alkyl having 5 to 18 carbon atoms, or form a heterocycle with N; X1 is a bond, or is —CO—O— whereby L2-CO—O—R2 is formed; X2 is S or O; L3 is a bond or a lower alkyl, or form a heterocycle with N; R3 is a lower alkyl; and R4 and R5 are the same or different, each a lower alkyl; or a pharmaceutically acceptable salt thereof.