Abstract: Provided are formulations, compositions and methods for delivering biological moieties such as modified nucleic acids into cells to modulate protein expression. Such compositions and methods include the delivery of biological moieties, and are useful for production of proteins.

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

Abstract: Provided herein are methods and compositions of a surrogate mRNA drug product. The surrogate mRNA drug product is made up of a physical property surrogate, a visual property surrogate, and a chemical property surrogate. The surrogate mRNA drug product has at least one quantitative or qualitative property such as viscosity, turbidity, density, and surface tension that is comparable to and matches the same property of a mRNA drug product comprised of mRNA in a lipid nanoparticle (LNP). The surrogate mRNA drug product, however, does not comprise mRNA or LNP.

Abstract: The present disclosure provides modified nucleosides, nucleotides, and nucleic acids, and methods of using thereof.

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 provides RNA vaccines for seasonal influenza virus as well as methods of using the vaccines.

Abstract: The invention relates to concatemeric peptide epitope RNAs, as well as methods and compositions thereof. mRNA vaccines are also provided according to the invention, including cancer vaccines.

Abstract: The disclosure relates to cancer ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines. In particular, the disclosure relates to concatemeric mRNA cancer vaccines encoding several cancer epitopes on a single mRNA construct, i.e. poly-epitope mRNA constructs or poly-neo-epitope constructs. The disclosure further relates to p53 and KRAS mutations, as well as incorporation of immune enhancers such as STING, e.g. mRNA constructs further encoding an immune stimulator or adjuvant. The disclosure further relates to inclusion of universal T cell epitopes, such as tetanus or diphtheria toxins to elicit an enhanced immune response.

Abstract: Aspects of the disclosure relate to methods of purifying mRNA by precipitating the mRNA, washing the precipitate to remove impurities and salts, and resuspending the washed mRNA to produce an mRNA composition. The disclosure describes reagents and methods useful for precipitation, washing, and resuspension of mRNA, and compositions produced by the methods described herein.

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 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: Provided herein are methods of preparing recycled template DNA solution from in vitro transcription (IVT) reaction product comprising template DNA. In some embodiments. the methods comprise removing mRNA from an IVT reaction product and removing one or more additional IVT reaction components and/or impurities to obtain a recycled template DNA solution. Also provided herein are systems for in vitro transcription (IVT) for producing mRNA.

Abstract: The disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. 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 disclosure relates to respiratory syncytial vims (RSV) ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines.

Abstract: Aspects of the disclosure relate to liquid chromatography (e.g., HPLC) methods which enable identification of one or more target nucleic acids in a mixture (e.g., pharmaceutical composition). The disclosure is based, in part, on methods that allow for addition of pharmaceutical compositions (e.g., lipid-based pharmaceutical compositions) directly onto a chromatographic column without the need for first separating target nucleic acids out of the composition. Accordingly, in some embodiments, methods described by the disclosure are useful for assessing the quality of pharmaceutical preparations comprising nucleic acids.

Abstract: The invention relates to mRNA therapy for the treatment of galactosemia type 1 (Gal-1). mRNAs for use in the invention, when administered in vivo, encode human galactose-1-phosphate uridylyltransferase (GALT), isoforms thereof, functional fragments thereof, and fusion proteins comprising GALT. 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 GALT expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient GALT activity in subjects, namely galactose-1-phosphate (Gal-1-P).

Abstract: Provided herein are methods of purifying nucleic acids (e.g., DNA) for gene synthesis using combinations of nucleases. Also provided are improved products for use in the production of RNA.

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

Abstract: The disclosure features methods of reducing or inhibiting an anti-drug antibody response in a subject, as well as methods of reducing or inhibiting unwanted immune cell activation in a subject to be treated with a messenger RNA (mRNA), comprising administering to the subject a mRNA, e.g., a chemically modified messenger RNA (mmRNA), encoding a polypeptide of interest, wherein the mRNA comprises at least one microRNA (miR) binding site for a miR expressed in immune cells, such as miR-126 binding site and/or miR-142 binding site, such that an anti-drug antibody response to the polypeptide or interest, or unwanted immune cell activation (e.g., B cell activation, cytokine secretion), is reduced or inhibited in the subject. The disclosure further provides therapeutic treatment regimens designed to reduce or inhibit ADA or unwanted immune cell activation (e.g., B cell activation, cytokine secretion) in a subject being treated with mRNA-based therapeutics.