Abstract: The disclosure features methods for treating solid tumor malignancies and lymphomas by administering LNP encapsulated mRNAs encoding human OX40L, IL-23 and IL-36? polypeptides alone or in combination with checkpoint blockade. The disclosure also features compositions for use in the methods.

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

Abstract: Aspects of the disclosure relate to methods for analyzing compositions comprising RNA species with unique nucleotide sequences for identification and/or ratio determination of RNAs. The disclosure is based, in part, on methods of cleaving identifying sequences from RNAs in a composition, and detecting the abundance of each identifying sequence to quantify the abundance of corresponding RNA species. Other aspects relate to methods for producing compositions comprising more than two RNA species, such as multivalent RNA compositions. The disclosure is based, in part, on methods of determining the proper amount of input DNA for in vitro transcription (IVT) reactions that will result in RNA being transcribed in a predetermined ratio. In some aspects, the disclosure relates to pharmaceutical compositions comprising multivalent RNA compositions produced by methods described, by the disclosure.

Abstract: The disclosure provides combination miRNA vaccines for respiratory viruses, such as influenza and coronaviruses (e.g., SARS-CoV-2) as well as methods of using the vaccines.

Abstract: Aspects of the present disclosure relate to methods of preparing lyophilized compositions comprising lipid, nanoparticles and nucleic acids. Other aspects relate to lyophilized compositions with low moisture contents and improved stability during long-term storage.

Abstract: The disclosure provides combination mRNA vaccines for respiratory viruses, as well as methods of using the vaccines.

Abstract: Provided herein are methods of purifying nucleic acids (e.g., mRNAs) from mixtures, including protease digestion of residual proteins, RNase III digestion of double-stranded RNAs, salt precipitation of mRNA, continuous removal of transcribed RNA, and improvement of column chromatography using high salt concentrations.

Abstract: The invention relates to compositions and methods for the manufacture and optimization of modified mRNA molecules via optimization of their terminal architecture.

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: The present application is directed to compositions comprising RNA having an open reading frame encoding an antibody heavy chain, an RNA having an open reading frame encoding an antibody light chain and an RNA having an open reading frame encoding an antibody J-chain, wherein the ratio of the RNAs is effective in producing an assembled antibody capable of forming a multimer. Compositions comprising RNA having an open reading frame encoding an IgG3 heavy chain, an RNA having an open reading frame encoding an antibody light chain, wherein the ratio of RNAs is effective in producing an assembled antibody are defined. Methods of producing therapeutic levels of IgA or IgM or IgG3 in vivo are also defined. The use of a lipid nanoparticle delivery vehicle is disclosed to administer the RNAs in vivo.

Abstract: Provided herein are methods of reducing adduct formation in lipid nanoparticle compositions comprising a polynucleotide, such as mRNA, and an ionizable lipid; also disclosed are lipid nanoparticle compositions having a reduced adduct content, and methods of detecting the adducts.

Abstract: The disclosure relates to pertussis nucleic acid vaccines, diphtheria nucleic acid vaccines, tetanus nucleic acid vaccines, and combination vaccines, as well as methods of using the vaccines and compositions comprising the vaccines.

Abstract: Provided herein are immunogenic compositions comprising mRNA encoding herpes simplex virus polypeptides, as well as methods of using the immunogenic compositions.

Abstract: Herpes simplex virus (HSV) ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines. In a preferred embodiment, the vaccine is formulated as a lipid nanoparticle comprising at least one cationic lipid.

Abstract: mRNAs containing an exogenous open reading frame (ORF) flanked by a 5? untranslated region (UTR) and a 3? UTR is provided, wherein the 5? and 3? UTRs are derived from a naturally abundant mRNA in a tissue. Also provided are methods for identifying the 5? and 3? UTRs, and methods for making and using the mRNAs.

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 disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include an ionizable lipid, a phospholipid, a first sterol or a tocopherol, and optionally a second sterol different from the first sterol. Nanoparticle compositions 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 present disclosure provides, in some aspects, variant RNA polymerases, the use of which increases transcription efficiency while reducing the number of double-stranded RNA contaminates and run-on transcripts produced during an in vitro transcription reaction.

Abstract: This disclosure relates to mRNA therapy for the treatment of hyperphenylalaninemias such as phenylketonuria (PKU). mRNAs for use in the invention, when administered in vivo, encode human phenylalanine hydroxylase (PAH), functional fragments thereof (e.g., those comprising the catalytic domain or the catalytic domain and the tetramerization domains), and fusion proteins comprising PAH. 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 PAH expression and/or activity in subjects. mRNA therapies of the invention further decrease abnormal accumulation of phenylalanine associated with deficient PAH activity in subjects.

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