Aspects of the disclosure relate to a nucleic acid comprising a heterologous nucleic acid insert flanked by interrupted self-complementary sequences, wherein one self-complementary sequence is interrupted by a cross-arm sequence forming two opposing, lengthwise-symmetric stem-loops, and wherein the other of the self-complementary sequences is interrupted by a truncated cross-arm sequence. Methods of delivering the nucleic acid to a cell are also provided.

Aspects of the disclosure relate to a nucleic acid comprising a heterologous nucleic acid insert flanked by interrupted self-complementary sequences, wherein one self-complementary sequence is interrupted by a cross-arm sequence forming two opposing, lengthwise-symmetric stem-loops, and wherein the other of the self-complementary sequences is interrupted by a truncated cross-arm sequence. Methods of delivering the nucleic acid to a cell are also provided.

Some embodiments of the invention include methods for treating an animal for cystic fibrosis comprising one or more administrations of one or more compositions comprising saracatinib. Other embodiments of the invention include treating an animal N for cystic fibrosis comprising one or more administrations of one or more compositions comprising saracatinib, optionally a corrector of ΔF508 CFTR, and optionally a potentiator of ΔF508 CFTR. Still other embodiments of the invention include methods for treating a human with cystic fibrosis caused by the F508 deletion mutation in the cystic fibrosis transmembrane conductance regulator (CFTR), comprising one or more administrations of one or more compositions comprising saracatinib, and optionally VX770, VX809, or both. Additional embodiments of the invention are also discussed herein.

The present invention provides, among other things, methods of treating cystic fibrosis, comprising a step of administering to a subject in need of treatment a composition comprising an mRNA encoding a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, wherein the mRNA encoding the CFTR protein comprises a polynucleotide sequence at least 80% identical to SEQ ID NO: 1, wherein the mRNA is at a concentration of at least 0.4 mg/mL, and wherein the step of administering comprises inhalation.

The present invention provides, among other things, methods of treating cystic fibrosis, comprising a step of administering to a subject in need of treatment a composition comprising an mRNA encoding a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, wherein the mRNA encoding the CFTR protein comprises a polynucleotide sequence at least 80% identical to SEQ ID NO: 1, wherein the mRNA is at a concentration of at least 0.4 mg/mL, and wherein the step of administering comprises inhalation.

Compounds of general formula (I) wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and X are as defined herein are inhibitors of the epithelial sodium channel (ENaC) and are useful for the treatment or prevention respiratory diseases and conditions, skin conditions and ocular conditions. ##STR00001##

Compounds of general formula (I) wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and X are as defined herein are inhibitors of the epithelial sodium channel (ENaC) and are useful for the treatment or prevention respiratory diseases and conditions, skin conditions and ocular conditions. ##STR00001##

Several embodiments of NO releasing compounds are disclosed. In some embodiments, the structures are covalently modified to store and release nitric oxide. Some embodiments pertain to methods of making and use of these structures. The compounds may be tailored to release nitric oxide in a controlled manner and can be useful, for example, for treating or preventing microbial infections, or reducing the microbial load of a microbial infection.

Three-dimensional printed antibiotic scaffolds are provided as well as methods of use thereof and methods of making.

The present invention relates to methods of using compounds of Formula I,

##STR00001## wherein R.sup.1a, R.sup.1b, R.sup.2, R.sup.3, R.sup.4, W, Y, and Z are as described herein, and pharmaceutically acceptable salts thereof. The compounds are potentiators of Cystic Fibrosis Transmembrane conductance Regulator (CFTR). The invention also discloses pharmaceutical compositions comprising the compound, optionally in combination with additional therapeutic agents, and methods of potentiating, in mammals, including humans, CFTR by administration of the compounds. These compounds are useful for the treatment of cystic fibrosis (CF), asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), constipation, Diabetes mellitus, dry eye disease, pancreatitis, rhinosinusitis, Sjögren's Syndrome, and other CFTR associated disorders.