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.

Abstract: The disclosure relates to respiratory syncytial virus (RSV) ribonucleic acid (RNA) vaccines as well as methods of using the vaccines and compositions comprising the vaccines. The vaccine can be formulated in a lipid nanoparticle.

Abstract: Aspects of the disclosure relate to liquid chromatography (e.g., HPLC) methods which enable high resolution separations of polynucleotides having hydrophobic portions (e.g., polyadenylated nucleic acids, such as mRNA) based upon the hydrophobic character of the molecules (e.g., polyA tail length). In some embodiments, the disclosure describes liquid chromatographic methods for separating a nucleic acid having a hydrophobic portion (e.g., a polyadenylated nucleic acid, such as an mRNA) from a complex mixture by a mobile phase system that comprises an ion pairing agent selected from Tris, inorganic cations (including e.g., Na, Li, K, ammonium, etc.), biological buffers (e.g., MOPS, HEPES, PIPES, etc.), and other charged or hydrophilic moieties, and lacks conventional ion pairing agents (e.g., Triethylammonium acetate, TEAA). Accordingly, in some embodiments methods described by the disclosure are useful for assessing the quality of pharmaceutical preparations comprising nucleic acids.

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: This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering nucleic acids in vivo. These compositions have reduced immune activation resulting in accelerated blood clearance and/or anti-drug antibodies and they have an improved toxicity profile and therapeutic index in vivo.

Abstract: The present invention relates to compositions and methods for the purification of ribonucleic acids including a polyA tail. The compositions and methods include a polystyrene divinylbenzene particle, a linker, and a poly-deoxythymidine oligonucleotide.

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

Abstract: The present disclosure relates to polynucleotides encoding tethered interleukin-12 (IL-12) polypeptides comprising an IL-12 polypeptide and a membrane domain. The present disclosure also relates to vectors comprising the polynucleotides; host cells comprising the polynucleotides or vectors, polypeptides encoded by the polynucleotides; compositions comprising the polynucleotides, vectors, host cells, or polypeptides and a delivery agent; and uses thereof, including treatment of cancer.

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

Abstract: The present disclosure relates to cap analogs, which can result in high levels of capping efficiency and transcription and improved translation efficiencies. The present disclosure also relates to methods useful for preparing cap analogs and using mRNA species containing such analogs, as well as kits containing the novel cap analogs.

Abstract: The disclosure relates to modified RNA molecules encoding VEGF-A polypeptides and formulations comprising the modified RNA. Aspects of the disclosure further relate to preparations and uses of formulations comprising the modified RNA in treating subjects suffering from diseases responsive to VEGF-A therapy.

Abstract: Aspects of the disclosure relate to liquid chromatography (e.g., HPLC) methods which enable high resolution separations of polynucleotides of various lengths, sequences, and/or base compositions in a highly tunable manner. In some embodiments, the disclosure describes liquid chromatographic methods for separating a nucleic acid (e.g., a polyadenylated nucleic acid, such as an mRNA) from a complex mixture by using multiple ion pairing agents in the same mobile phase system. 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 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: This disclosure relates mRNA therapy for the treatment of ornithine transcarbamylase deficiency (OTCD). mRNAs for use in the invention, when administered in vivo, encode human ornithine transcarbamylase (OTC), isoforms thereof, functional fragments thereof, and fusion proteins comprising OTC. 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 OTC expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic ammonia associated with deficient OTC activity in subjects.

Abstract: The present disclosure provides methods and compositions for high fidelity in vitro transcription reactions.

Abstract: Disclosed herein are methods for purifying RNA comprising poly A. Also disclosed herein are compositions such as surfaces and oligonucleotides for purifying RNA comprising polyA. Other embodiments are also disclosed. Commercially-available resins having polythymidine oligonucleotide ligands typically contain less than 30 thymidine (2?deoxy) residues and some commercial resin suppliers utilize a distribution of dT chain lengths, not of a discreet length.

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

Abstract: Provided herein, in some embodiments, are vaccines (and vaccination methods) that include a ribonucleic acid (RNA) polynucleotide encoding a human metapneumovirus (hMPV) F protein and a RNA polynucleotide encoding a human parainfluenza virus 3 (hPIV3) F protein.