The present invention provides compositions and methods for reprogramming somatic cells using purified RNA preparations comprising single-strand mRNA encoding an iPS cell induction factor. The purified RNA preparations are preferably substantially free of RNA contaminant molecules that: i) would activate an immune response in the somatic cells, ii) would decrease expression of the single-stranded mRNA in the somatic cells, and/or iii) active RNA sensors in the somatic cells. In certain embodiments, the purified RNA preparations are substantially free of partial mRNAs, double-stranded RNAs, un-capped RNA molecules, and/or single-stranded run-on mRNAs.

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding a cystic fibrosis transmembrane conductance regulator (CFTR) polypeptide (e.g., a human CFTR polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of a chronic lung disease, such as cystic fibrosis); and articles of manufacture or kits thereof.

This disclosure relates to delivery vehicles comprising payload molecules, e.g., mRNA or gene editing therapeutics for the treatment of cystic fibrosis (CF). Nucleic acid therapeutics (e.g., mRNAs) for use in the invention, when administered in vivo, encode cystic fibrosis transmembrane conductance regulator (CFTR). Nucleic acid therapeutics (e.g., mRNAs) of the disclosure increase and/or restore deficient levels of CFTR expression and/or activity in subjects. Nucleic acid therapeutics (e.g., mRNAs) of the disclosure further decrease abnormal accumulation of ammonia associated with deficient CFTR activity in subjects.

The present invention provides compositions and methods for reprogramming somatic cells using purified RNA preparations comprising single-strand mRNA encoding an iPS cell induction factor. The purified RNA preparations are preferably substantially free of RNA contaminant molecules that: i) would activate an immune response in the somatic cells, ii) would decrease expression of the single-stranded mRNA in the somatic cells, and/or iii) active RNA sensors in the somatic cells. In certain embodiments, the purified RNA preparations are substantially free of partial mRNAs, double-stranded RNAs, un-capped RNA molecules, and/or single-stranded run-on mRNAs.

Nucleic acid molecules are provided herein that can be used, for example, to treat cancer or infections, or to induce an immune response in a subject, or to deliver or express a target molecule in or from a cell.

Compositions and kits including an agent that inhibits the interaction between Disabled-2 and mutant CFTR proteins, optionally in combination with a CFTR corrector, CFTR potentiator, CAL inhibitor, mucolytic, anti-inflammatory agent or a combination thereof are provided as are methods for preventing or treating cystic fibrosis.

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding a cystic fibrosis transmembrane conductance regulator (CFTR) polypeptide (e.g., a human CFTR polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of a chronic lung disease, such as cystic fibrosis); and articles of manufacture or kits thereof.

The present disclosure is directed in part to methods of detecting and quantifying cystic fibrosis transmembrane conductance regulator (CFTR) protein expression in a sample, e.g., by an Enzyme-Linked Immunosorbent Assay (ELISA) or an AlphaLISA, a fusion polypeptide capable of binding to a capture antibody and a detection antibody, and a kit for performing an ELISA or an AlphaLISA to detect CFTR protein.

This invention provides a range of translatable messenger UNA (mUNA) molecules. The mUNA molecules can be translated in vitro and in vivo to provide an active polypeptide or protein, or to provide an immunization agent or vaccine component. The mUNA molecules can be used as an active agent to express an active polypeptide or protein in cells or subjects. Among other things, the mUNA molecules are useful in methods for treating rare diseases.

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding a cystic fibrosis transmembrane conductance regulator (CFTR) polypeptide (e.g., a human CFTR polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of a chronic lung disease, such as cystic fibrosis); and articles of manufacture or kits thereof.