Abstract: The disclosure relates to Epstein-Barr virus ribonucleic acid vaccines as well as methods of using the vaccines and compositions comprising the vaccines.

Abstract: Provided herein are methods of making trinucleotides and tetranucleotides for use as 5? mRNA caps. The methods utilize a novel “top-down” strategy and provide for synthesis of oligonucleotides with higher yields and increased efficiency compared to traditional methods. A key step of the methods disclosed, herein can also be adapted to utilize a “one-pot” approach, resulting in an increase in the yield of the final oligonucleotide product.

Abstract: This disclosure provides methods and compositions related to messenger ribonucleic acid (mRNA) vaccines for Lyme disease and related methods of prevention. The mRNA vaccines comprise an mRNA comprising an open reading frame(s) encoding for a protein comprising a Borrelia outer surface protein A (OspA) extracellular domain. In some aspects of the disclosure, the mRNA vaccines comprise mRNA polynucleotides collectively encoding for at least seven different Borrelia outer surface protein A (OspA) extracellular domains.

Abstract: This disclosure relates to delivery vehicles comprising payload molecules, e.g., mRNA or gene editing therapeutics for the treatment of cystic fibrosis (CF). Nucleic acid therapeutics (e.g., mRNAs) for use in the invention, when administered in vivo, encode cystic fibrosis transmembrane conductance regulator (CFTR). Nucleic acid therapeutics (e.g., mRNAs) of the disclosure increase and/or restore deficient levels of CFTR expression and/or activity in subjects. Nucleic acid therapeutics (e.g., mRNAs) of the disclosure further decrease abnormal accumulation of ammonia associated with deficient CFTR activity in subjects.

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: Described are methods and apparatuses for isolating and purifying mRNA using Immobilized Metal Affinity Chromatography (IMAC). The methods and apparatuses use IMAC matrices and IMAC conditions designed to selectively bind and elute mRNA, and are useful, for example, for isolating and purifying mRNA from in vitro-transcribed compositions. The methods and apparatuses also are useful for isolating and purifying linear or circular RNA having a poly(A) tail.

Abstract: The disclosure provides coronavirus mRNA vaccines, including vaccines directed against spike proteins of one or more variant strains of SARS-CoV-2, as well as methods of using the vaccines.

Abstract: The invention 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: Aspects of the disclosure relate to compositions of messenger RNA vaccines and methods of administration thereof. Compositions provided herein include one or more RNA polynucleotides having an open reading frame encoding a norovirus capsid protein (VP1).

Abstract: Aspects of the disclosure relate to invitro transcription reactions comprising an initiator oligonucleotide, a deoxyribonucleic acid (DNA), a ribonucleic acid (RNA) polymerase, and nucleoside triphosphates (NTPs), wherein the initiator oligonucleotide comprises at least four contiguous nucleotides. In some embodiments, the disclosure relates to new and improved compositions of initiator oligonucleotides.

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 invention relates to compositions and methods for the preparation, manufacture and therapeutic use ribonucleic acid vaccines comprising polynucleotide molecules encoding one or more influenza antigens, such as hemagglutinin antigens.

Abstract: Stabilized formulations of nucleic acids, including lipid nanoparticle formulations which encapsulate nucleic acids, are provided. Methods of making and of use of the formulations stabilized by chemical compounds are also provided.

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.