46 results about "Cftr proteins" patented technology

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.

A combination therapy and kit including an agent that inhibit the interaction between CAL and mutant CFTR proteins, in combination with a CFTR corrector, CFTR potentiator, mucolytic, anti-inflammatory agent or a combination thereof are provided as is a method for preventing or treating cystic fibrosis.

The present invention features compositions and methods for increasing the cell surface expression of degradation-prone CFTR proteins and preventing or treating cystic fibrosis. The invention provides peptides and peptidomimetics that selectively inhibit the interaction between CAL and mutant CFTR proteins, thereby stabilizing the CFTR and facilitating transport of the same to the cell surface.

The present invention relates to nucleic acid molecules comprising certain truncated forms of the human cytomegalovirus (CMV) immediate-early enhancer-promoter, either alone or operably linked to transgenes of interest, including those encoding partially-deleted CFTR proteins. This invention further relates to vectors comprising these nucleic acid molecules and host cells transformed by such vectors. The nucleic acid molecules, vectors and transformed host cells of the present invention are useful for treating a variety of genetic, metabolic and acquired diseases, including inter alia cystic fibrosis (CF) airway disease.

The present invention provides methods and compositions for enhancing channel activity to the mutant cystic fibrosis trans-membrane conductance regulator protein (CFTR). The compositions of the invention comprise polypeptides containing CFTR sub-domains that are designed to mimic the folding defect of the full length mutant CFTR proteins, resulting in competitive binding to cytoplasmic chaperones such as Hsc / Hsp7O and Hdj2. The methods of the invention comprise transduction, or recombinant expression, of CFTR polypeptides in a cell expressing mutant CFTR. The presence of the CFTR polypeptide results in a dominant effect whereby the CFTR polypeptide competes with the endogenously expressed mutant CFTR for binding to cytoplasmic chaperones such as Hsc / Hsp70 and Hdj2. Mutant CFTR proteins include, but are not limited to, DeltaF508 CFTR. The present invention is based on the discovery that reduced binding of cytoplasmic chaperones to the endogenous DeltaF508 CFTR, mediated by the presence of CFTR polypeptides, results in restoration of plasma membrane localization and channel activity. The methods and compositions of the invention can be used to restore channel activity in cystic fibrosis subjects carrying genetic defects in the CFTR gene, such as for example, DeltaF508 CFTR.

The present disclosure provides a method of treating diseases or disorders associated with CFTR protein dysfunction, including Cystic Fibrosis, by administering stable, long-lasting vasoactive intestinal peptide therapeutic agents. These agents include one or more elastin-like peptides and can be administered at a low-dose.

The present invention features compositions and methods for increasing the cell surface expression of degradation-prone CFTR proteins and preventing or treating cystic fibrosis. The invention provides peptides and peptidomimetics that selectively inhibit the interaction between CAL and mutant CFTR proteins, thereby stabilizing the CFTR and facilitating transport of the same to the cell surface.

The present invention relates to nucleic acid molecules comprising certain truncated forms of the human cytomegalovirus (CMV) immediate-early enhancer-promoter, either alone or operably linked to transgenes of interest, including those encoding partially-deleted CFTR proteins. This invention further relates to vectors comprising these nucleic acid molecules and host cells transformed by such vectors. The nucleic acid molecules, vectors and transformed host cells of the present invention are useful for treating a variety of genetic, metabolic and acquired diseases, including inter alia cystic fibrosis (CF) airway disease.

The present invention features compositions and methods for increasing the cell surface expression of degradation-prone CFTR proteins and preventing or treating cystic fibrosis. The invention provides peptides and peptidomimetics that selectively inhibit the interaction between CAL and mutant CFTR proteins, thereby stabilizing the CFTR and facilitating transport of the same to the cell surface.

The present invention relates to the use of agents, which are 1-phenyl-2-pyridinyl alkyl alcohol derivatives, for the prevention and / or treatment of cystic fibrosis in a subject, wherein the subject is characterized by at least one mutation in the gene encoding the CFTR protein, wherein the at least one mutation is causative for incorrect folding and / or processing of the CFTR protein. By the use of the compound according to the present invention, cystic fibrosis in the subject may be prevented or treated. The agent to be used according to the present invention has the capacity to restore the presence of the mutant CFTR protein at the cell surface, and thus act as CFTR correctors. The agent to be used according to the present invention may be administered to a subject in need thereof alone or in combination therapy with other agents, and is suitably administered by inhalation.

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, 5495P, A534P, I539T, G550E, G551D, R553Q, R555K, Q637R, 51255L, K1334G, 51359A, E1371Q, H14025, 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.

A combination therapy and kit including an agent that inhibit the interaction between CAL and mutant CFTR proteins, in combination with a CFTR corrector, CFTR potentiator, mucolytic, anti-inflammatory agent or a combination thereof are provided as is a method for preventing or treating cystic fibrosis.

The present invention relates to the use of agents, which are 1-phenyl-2-pyridinyl alkyl alcohol derivatives, for the prevention and / or treatment of cystic fibrosis in a subject, wherein the subject is characterized by at least one mutation in the gene encoding the CFTR protein, wherein the at least one mutation is causative for incorrect folding and / or processing of the CFTR protein. By the use of the compound according to the present invention, cystic fibrosis in the subject may be prevented or treated. The agent to be used according to the present invention has the capacity to restore the presence of the mutant CFTR protein at the cell surface, and thus act as CFTR correctors. The agent to be used according to the present invention may be administered to a subject in need thereof alone or in combination therapy with other agents, and is suitably administered by inhalation.

The present disclosure provides methods for treating Cystic Fibrosis in a subject by administering to the subject a corrector agent capable of acting through MSD1 during the biosynthesis of CFTR protein. The disclosure also provides methods of screening for new corrector agents capable of acting through MSD1 during the biosynthesis of a CFTR protein.

A combination therapy and kit including an agent that inhibit the interaction between CAL and mutant CFTR proteins, in combination with a CFTR corrector, CFTR potentiator, mucolytic, anti-inflammatory agent or a combination thereof are provided as is a method for preventing or treating cystic fibrosis.

The present invention relates to novel protein regulators capable of altering the function of mutant CFTR proteins, and their use in the treatment of diseases associated with dysfunctional CFTR proteins. The present invention provides compositions, pharmaceutical formulations and methods for correcting cellular changes in mutant CFTR proteins, wherein the CFTR mutation is the mutation ΔF508-CFTR, or another Type II mutation.

The present disclosure provides a technique for inhibiting ubiquitin ligase RFFL function and improving the plasma-membrane expression of a mutant CFTR protein. The present disclosure also provides a novel therapeutic agent for CF.　The present inventors have found that a modified oligonucleotide, or a salt thereof, having a specific base sequence and a modified structure, can inhibit ubiquitin ligase RFFL function and improve the plasma-membrane expression of a mutant CFTR protein.

The present disclosure relates to compositions for the restoration of porosome faction, comprising isolated porosome complexes that include a functional CFTR protein and a pharmaceutically acceptable excipient. These compositions are specifically formulated for inhaled or nasal administration, enabling delivery of the functional porosome complexes directly to the airway epithelium. By restoring the presence of functional CFTR within the porosome complex at the plasma membrane, the disclosed compositions address the underlying secretory defect in cystic fibrosis and provide a novel therapeutic approach for patients affected by this disease.

The present invention relates to novel protein modulators capable of altering function of the mutant CFTR protein and their use for treating diseases associated with CFTR protein malfunction. The invention provides compositions, pharmaceutical preparations and methods of correcting the cellular alteration of a mutant CFTR protein wherein the CFTR mutation is a mutation delta F508-CFTR, or another mutation of class II.

The subject invention concerns materials and methods for detecting the interaction of CFTR proteins. In one embodiment, the method can be used to determine whether one CFTR polypeptide interacts with a second CFTR polypeptide. The subject invention also concerns materials and methods for screening for drugs or compositions that can restore or enhance interaction of CFTR proteins containing mutation(s) that reduce or prevent dimerization of the proteins. The assay of the present invention can be used to screen a large number of compounds in a high throughput format. The subject invention also pertains to host cells useful in the methods of the invention. The subject invention also concerns compositions and methods for treating patients afflicted with cystic fibrosis.

To provide adeno-associated variants, formulations and methods for pulmonary delivery.SOLUTION: The present disclosure provides variant AAV capsid proteins that confer tropism for lung cells, as well as recombinant adeno-associated viruses comprising the variant AAVs and pharmaceutical compositions comprising the same, and their use in the delivery of heterologous nucleic acids to lung cells for the treatment of lung disorders. (ii) nucleic acids comprising, from 5 ' to 3 ', (a) AAV2 terminal repeats, (b) a promoter, (c) a nucleotide sequence encoding a human cystic fibrosis transmembrane conductance regulator (CFTR) or a biologically active truncated CFTR lacking amino acids 708 to 759 of the human CFTR sequence, (d) a poly-adenylation sequence, and (e) AAV2 terminal repeats.SELECTED DRAWING: None

A combination therapy and kit including an agent that inhibit the interaction between CAL and mutant CFTR proteins, in combination with a CFTR corrector, CFTR potentiator, mucolytic, anti-inflammatory agent or a combination thereof are provided as is a method for preventing or treating cystic fibrosis.

Cystic Fibrosis (CF) is a recessive, lethal genetic disease in which many patients have inherited DNA mutations that create a CFTR protein that is produced, but ineffective in its function. The present disclosure generally pertains to methods and products for increasing CFTR production through the use of a CRISPR / dCas9 system. This disclosure describes such system, which comprises gRNA configured to target the CFTR domain and dCas9 configured to upregulate expression of the gRNA target, and methods of using the same.

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 invention relates to novel protein modulators capable of altering function of the mutant CFTR protein and their use for treating diseases associated with CFTR protein malfunction. The invention provides compositions, pharmaceutical preparations and methods of correcting the cellular alteration of a mutant CFTR protein wherein the CFTR mutation is a mutation delta F508-CFTR, or another mutation of class II.

The present disclosure provides methods for treating Cystic Fibrosis in a subject by administering to the subject a corrector agent capable of acting through MSD1 during the biosynthesis of CFTR protein. The disclosure also provides methods of screening for new corrector agents capable of acting through MSD1 during the biosynthesis of a CFTR protein.

Provided herein are amino acid compositions useful for increasing the translocation of the cystic fibrosis transmembrane conductance (CFTR) protein from the cytoplasm to the plasma membrane, particularly in epithelial cells. Methods for increasing the concentration of CFTR in the plasma membrane, increasing chloride ion transport, and increasing water transport are also provided. These compositions and methods are useful in treating cystic fibrosis in subjects bearing one or more mutations in the CFTR protein. Use of these compositions for the treatment of cystic fibrosis and in the preparation of a medicament for the treatment of cystic fibrosis are also encompassed herein.

The present disclosure provides a method of treating diseases or disorders associated with CFTR protein dysfunction, including Cystic Fibrosis, by administering stable, long-lasting vasoactive intestinal peptide therapeutic agents. These agents include one or more elastin-like peptides and can be administered at a low-dose.

In some aspects, provided herein are compositions, methods, and kits relating to an agent modulates expression of a CFTR protein. An agent provide herein can modify the CFTR gene or modulate process of the CFTR pre-mRNA. In some embodiments, the compositions, methods, and kits provided herein are applicable for treatment of cystic fibrosis.