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: The present invention provides, among other things, improved pharmaceutical compositions comprising codon-optimized mRNA encoding a peptide or polypeptide encapsulated in a lipid nanoparticle comprising one or more of the cationic lipids that are particularly effective for pulmonary delivery.

Abstract: Provided is a method for inducing innate apolipoprotein B editing catalytic protein (APOBEC) driven C>U RNA deamination of RNA in a cell comprising contacting the cell with an effective amount of atpenin A5 with or without interferon. Specifically, APOBEC3A is a cytidine deaminase enzyme that edits RNA transcripts of hundreds of cellular genes upon stimulation of innate immune cells by low oxygen tension (hypoxia) or antiviral factor interferon. Atpenin A5 induces APOBEC3A-mediated RNA editing in normoxia to levels comparable to those seen in hypoxia. The method can be used to treat viral conditions.

Abstract: Provided are methods for inhibiting cancer cell growth comprising contacting the cancer cell with an agent which inhibits the expression of the gene, or the activity of, apolipoprotein B editing catalytic 3G (APOBEC3G). Also provided are methods for identifying agents which can induce or inhibit C>U deamination in RNA driven by apolipoprotein B editing catalytic proteins. The method comprises contacting APOBEC3G with a suitable RNA substrate and determining the extent of C>U deamination under conditions which induce APOBEC driven C>U deamination.

Abstract: Provided is a method for inducing innate apolipoprotein B editing catalytic protein (APOBEC) driven C>U RNA deamination of RNA in a cell comprising contacting the cell with an effective amount of atpenin A5 with or without interferon. Specifically, APOBEC3A is a cytidine deaminase enzyme that edits RNA transcripts of hundreds of cellular genes upon stimulation of innate immune cells by low oxygen tension (hypoxia) or antiviral factor interferon. Atpenin A5 induces APOBEC3A-mediated RNA editing in normoxia to levels comparable to those seen in hypoxia. The method can be used to treat viral conditions.

Abstract: Provided are methods for identifying agents which can induce or inhibit C>U deamination in RNA driven by apolipoprotein B editing catalytic proteins. The method comprises contacting APOBEC3A or APOBEC3G with a suitable RNA substrate and determining the extent of C>U deamination under conditions which induce APOBEC driven C>U deamination.