Gene-therapeutic DNA vectors based on the VTvaf17 gene-therapeutic DNA vector have been created for the treatment of diseases characterized by impaired mucociliary transport and mucolytic function and the development of mucostasis, including cystic fibrosis. The gene therapy DNA vector contains the coding region of the CFTR therapeutic gene, or the NOS1 therapeutic gene, or the AQ1 therapeutic gene, or the AQ3 therapeutic gene, or the AQ5 therapeutic gene. Methods for their preparation or use are proposed, as well as strains for the production of a gene therapy vector.

Materials, formulations, production methods, and methods for delivery of CFTR mRNA for induction of CFTR expression, including in the mammalian lung are provided. The present invention is particularly useful for treating cystic fibrosis.

The present disclosure provides a variant AAV capsid protein that confers tropism to lung cells and recombinant adeno-associated viruses comprising the variant AAV and pharmaceutical compositions comprising same and their use in the delivery of heterologous nucleic acids to lung cells for the treatment of pulmonary disorders.

This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

Nucleases and methods of using these nucleases for alteration of a CFTR gene and generation of cells and animal models.

This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

The present invention relates to a nucleotide-modified messenger RNA for the permanent correction of a genetic alteration on a DNA. The invention further relates to a nucleotide-modified messenger RNA in combination with a repair template. It also relates to a pharmaceutical composition. It finally relates to methods for the correction of a genetic alteration on a DNA.

Provided herein are recombinant AAV vectors, AAV viral vectors, and capsid proteins for improved gene therapy, and methods for their manufacture and use.

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 invention is directed to nanoparticles for delivery of nucleic acids to target cells of interest for transfection and expression. The nanoparticles typically include a complex of a cationic peptide bound to a protective hydrophilic polymer through a chelator. The nucleic acid is held to the complex by ionic interactions with the cationic peptide. The chelator is adapted to allow release of the hydrophilic polymer in a time frame suitable to facilitate transfection with the nanoparticle at the target cell surface.