The disclosure relates to broad spectrum influenza virus ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccine. In a preferred embodiment, the vaccine is formulated as a lipid nanoparticle comprising at least one cationic lipid.

Nucleic acids encoding fusion proteins that contain an unwanted antigen and a leader sequence for cell secretion are described. Also described are expression cassettes, vectors, cells, and cell lines containing the nucleic acids, as well as methods of using the nucleic acids to treat autoimmune, allergic and other diseases and disorders, such as multiple sclerosis.

Nucleic acids encoding fusion proteins that contain an unwanted antigen and a leader sequence for cell secretion are described. Also described are expression cassettes, vectors, cells, and cell lines containing the nucleic acids, as well as methods of using the nucleic acids to treat autoimmune, allergic and other diseases and disorders, such as multiple sclerosis.

Provided are compounds, methods, and pharmaceutical compositions for modulating SCN1A RNA and/or protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a developmental or epileptic encephalopathic disease, such as Dravet Syndrome. Such symptoms include seizures, sudden unexpected death in epilepsy, status epilepticus, behavioral and developmental delays, movement and balance dysfunctions, orthopedic conditions, motor and cognitive dysfunctions, delayed language and speech issues, visual motor integration dysfunctions, visual perception dysfunctions, executive dysfunctions, growth and nutrition issues, sleeping difficulties, chronic infections, sensory integration disorders, and dysautonomia.

Provided are compounds, methods, and pharmaceutical compositions for modulating SCN1A RNA and/or protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a developmental or epileptic encephalopathic disease, such as Dravet Syndrome. Such symptoms include seizures, sudden unexpected death in epilepsy, status epilepticus, behavioral and developmental delays, movement and balance dysfunctions, orthopedic conditions, motor and cognitive dysfunctions, delayed language and speech issues, visual motor integration dysfunctions, visual perception dysfunctions, executive dysfunctions, growth and nutrition issues, sleeping difficulties, chronic infections, sensory integration disorders, and dysautonomia.

Provided are octavalent influenza vaccine compositions comprising eight mRNA, each mRNA comprising an open reading frame encoding a different influenza antigen. Also provided are lipid nanoparticles (LNPs) for delivering said mRNA.

Provided are octavalent influenza vaccine compositions comprising eight mRNA, each mRNA comprising an open reading frame encoding a different influenza antigen. Also provided are lipid nanoparticles (LNPs) for delivering said mRNA.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

The present invention relates to alkyne- and/or azide-modified mRNA, processes for producing such modified mRNA, cells which are transfected to include the modified mRNA, pharmaceutical compositions containing the modified mRNA or cells including the modified mRNA, and to uses of such mRNA, cells or pharmaceutical compositions in mRNA based therapeutic and/or prophylactic applications.