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 is directed to modified CFTR proteins or fragments thereof that contain single or multiple amino acid mutations to improve the structural stability of such CFTR proteins and/or fragments. Specifically, the modified CFTR proteins or fragment thereof differ from the wild-type human CFTR protein or fragment thereof by the presence of four or more mutations selected from V150D, M470V, S492P, F494N, S495P, A534P, I539T, G550E, G551D, R553Q, R555K, Q637R, S1255L, K1334G, S1359A, E1371Q, H1402S, Q1411D, and any combination thereof, such that the stability of the polypeptide is increased relative to that of the wild-type human CFTR polypeptide or fragment thereof.

Described herein are lipid nanoparticles comprising cationic lipids and other lipids and also comprising engineered nucleases facilitate transfer of nucleic acids to cells.

The present disclosure relates to materials, formulations, production methods, and methods for delivery of CFTR mRNA, including but not limited to chemically modified mRNA for induction of CFTR expression, including in the mammalian lung. The present invention is particularly useful for treating cystic fibrosis, but is also useful in the treatment of diseases related to CFTR gene.

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.

The present invention provides, among other things, an improved method of treating cystic fibrosis (CF) in a human subject. The method comprises administering a composition comprising an mRNA encoding a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein at a concentration of 0.5 mg/mL or greater to a human subject via nebulization. The composition is aerosolized using a nebulizer and a nominal dose of the mRNA is administered to the human subject via the nebulizer over a period of time, typically at least 30 minutes, at a suitable nebulization rate, e.g., at least 0.2 mL/minute.

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

The present invention is directed to synthetic anti-inflammatory peptides and use thereof in the treatment and prevention of inflammatory and fibrotic conditions. Specifically, the invention relates in some embodiments to short isolated peptides having the amino acid sequence Phe-Lys-Glu (FKE), Tyr-Lys-Glu (YKE) or comprising a plurality of these sequences that may be flanked by Ala/Gly (A/G) linkers. The invention further relates in some embodiments to methods for inhibiting scar formation and for treating and alleviating IL-10 dependent conditions.

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.

Provided herein are polynucleotides, lentiviral vectors, pharmaceutical compositions, and methods of making and using the same, e.g., for treatment of cystic fibrosis (CF).