Abstract: Provided are novel lipid nanoparticles for delivering nucleic acids such as mRNA. Also provided are methods of making and using lipid nanoparticles for delivering nucleic acids such as mRNA.

Abstract: Provided are novel lipid nanoparticles for delivering nucleic acids such as mRNA. Also provided are methods of making and using lipid nanoparticles for delivering nucleic acids such as mRNA.

Abstract: The present invention provides methods for preparing optimized DNA sequences as templates for in vitro transcription of mRNA. These DNA sequences are optimized to avoid premature termination of transcription by RNA polymerase. The invention also provides methods for preparing optimized DNA sequences that include one or more termination signal at their 3? end to reduce or prevent non-templated “runoff” transcription.

Abstract: The present invention provides, among other things, method of treating an immune disease in a subject, the method comprising: administering to a subject in need thereof one or more mRNAs encoding a heavy chain and a light chain of an antibody that binds to a protein target selected from IL-4, IL-5, IL-6, IL-9, IL-13, IL-25, or IL-33, IL-4R, IL-5R, IL-6R, IL-9R, IL-13R, IL-25R or IL-33R, and wherein the one or more mRNAs are encapsulated in a lipid nanoparticle (LNP). The present invention also provides, among other things, a composition comprising one or more mRNAs encoding a heavy chain and a light chain of an antibody that binds a protein target selected from IL-4, IL-5, IL-6, IL-9, IL-13, IL-25, or IL-33, IL-4R, IL-5R, IL-6R, IL-9R, IL-13R, IL-25R or IL-33R, and wherein the one or more mRNAs are encapsulated in a lipid nanoparticle (LNP).

Abstract: A method for generated an optimized nucleotide sequence is provided. The method comprises at least normalizing a codon usage table and selection of codons for a given amino acid sequence based on the usage frequency of the codons in the normalized codon usage table. The method may comprise generating a list of a plurality of optimized nucleotide sequences encoding the amino acid sequence, filtering the list of optimized nucleotide sequences, synthesizing one or more optimized nucleotide sequence, and/or administering one or more synthesized optimized nucleotide sequence.

Abstract: The present invention provides, among other things, methods and compositions for treating primary ciliary dyskinesia (PCD) based on mRNA therapy. The compositions used in treatment of PCD comprise an mRNA comprising a dynein axonemal intermediate chain 1 (DNAI1) coding sequence and are administered at an effective dose and an administration interval such that at least one symptom or feature of PCD is reduced in intensity, severity, or frequency or has a delayed onset. mRNAs with optimized DNAI1 coding sequences are provided that can be administered without the need for modifying the nucleotides of the mRNA to achieve sustained in vivo function.

Abstract: The present invention provides, among other things, improved methods and pharmaceutical compositions for treating cystic fibrosis based on codon optimized mRNA encoding a wild-type Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein.

Abstract: Provided are novel lipid nanoparticles for delivering nucleic acids such as mRNA. Also provided are methods of making and using lipid nanoparticles for delivering nucleic acids such as mRNA.

Abstract: Provided are novel lipid nanoparticles for delivering nucleic acids such as mRNA. Also provided are methods of making and using lipid nanoparticles for delivering nucleic acids such as mRNA.

Abstract: Provided are novel lipid nanoparticles for delivering nucleic acids such as mRNA. Also provided are methods of making and using lipid nanoparticles for delivering nucleic acids such as mRNA.