Abstract: This disclosure relates to mRNA therapy for the treatment of propionic acidemia (PA). mRNAs for use in the invention, when administered in vivo, encode human propionyl-CoA carboxylase alpha (PCCA) and/or human propionyl-CoA carboxylase beta (PCCB), and isoforms thereof, functional fragments thereof, and fusion proteins comprising PCCA and/or PCCB. 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 propionyl-CoA carboxylase (PCC) expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of disease-associated toxic metabolites associated with deficient PCCA or PCCB activity, in subjects.

Abstract: 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.

Abstract: Aspects of the disclosure relate to mRNAs comprising a relatively low abundance of cytidine: adenosine (CA) dinucleotides that benefit from increased stability relative to mRNAs containing more CpA dinucleotides. The disclosure also relates to methods of modifying an mRNA sequence to improve stability. In some aspects, the disclosure relates to mRNAs comprising modified mRNA sequences with relatively reduced numbers of CpA dinucleotides, and compositions comprising mRNAs with relatively reduced numbers of CpA dinucleotides.

Abstract: The disclosure relates to cancer ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines.

Abstract: The disclosure relates to cancer ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines.

Abstract: Provided herein are compositions and methods of reducing adduct formation.

Abstract: Some aspects of the disclosure relate to vaccines (e.g., RNA vaccines (e.g., mRNA vaccines)) for seasonal influenza viruses as well as methods of using the vaccines. Also described are combination vaccines (e.g., RNA vaccines (e.g., mRNA vaccines)) for seasonal influenza viruses and other respiratory viruses (e.g., respiratory syncytial viruses and coronaviruses), as well as methods of using the vaccines.

Abstract: The disclosure relates to cancer ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines.

Abstract: This disclosure relates to mRNA therapy for the treatment of maple syrup urine disease (MSUD). mRNAs for use in the invention, when administered in vivo, encode branched chain ?-ketoacid dehydrogenase complex (BCKDC) E1?, E1?, or E2mRNA therapies of the disclosure increase and/or restore deficient levels of E1?, E1?, or E2 expression and/or BCKDC activity in subjects. mRNA therapies of the invention further decrease abnormal accumulation of branched chain amino acids associated with deficient BCKDC activity in subjects.

Abstract: The disclosure relates to ribonucleic acid (RNA) vaccines and combination vaccines, as well as methods of using the vaccines and compositions comprising the vaccines. Specific embodiments relate to RNA betacoronavirus vaccines formulated in a lipid nanoparticle.

Abstract: Aspects of the disclosure relate to nucleic acid vaccines. The vaccines include at least one RNA polynucleotides having a open reading frame encoding at least varicella zoster virus (VZV) antigen. Methods for preparing and using such vaccines are also described.

Abstract: Personalized mRNA cancer vaccines, as well as methods for their optimization and for their use in subjects are provided. In some embodiments, personalized mRNA cancer vaccines and their uses are provided for subjects having particular characteristics, e.g., the presence of certain biomarkers.

Abstract: The disclosure relates to ribonucleic acid (RNA) vaccines and combination vaccines, as well as methods of using the vaccines and compositions comprising the vaccines. Specific embodiments relate to RNA betacoronavirus vaccines formulated in a lipid nanoparticle.

Abstract: The disclosure relates to ribonucleic acid (RNA) vaccines and combination vaccines, as well as methods of using the vaccines and compositions comprising the vaccines. Specific embodiments relate to RNA betacoronavirus vaccines formulated in a lipid nanoparticle.

Abstract: The present invention relates to a rapid, high-fidelity process to support synthesis of genes for in vitro transcription of modified messenger RNA. In this process, sequence errors resulting from amplification with oligonucleotides comprising inherent errors are significantly reduced.

Abstract: The disclosure features novel lipids and compositions involving the same. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

Abstract: The invention relates to compositions and methods for the preparation, manufacture, and therapeutic use of ribonucleic acid vaccines comprising polynucleotide molecules encoding one or more antigens.

Abstract: The disclosure relates to cancer ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines.

Abstract: Provided herein are methods for purifying an ionizable amino lipid (IAL) composition comprising impurities that may react with polynucleotides, such as mRNA. Methods for purifying IAL compositions comprise one or more scavenging-removal steps to selectively remove reactive impurities.