Compounds are provided that are modulators of the C5a receptor. The compounds are substituted piperidines and are useful in pharmaceutical compositions, methods for the treatment of diseases and disorders involving the pathologic activation of C5a receptors.

The present invention is directed to a novel treatment for Wolfram Syndrome or heterozygous wolframin, to methods of treatment in order to delay, inhibit, ameliorate and/or reduce the likelihood of symptomology of a patient with Wolfram Syndrome or heterozygous wolframin.

The present invention is directed to a novel treatment for Wolfram Syndrome or heterozygous wolframin, to methods of treatment in order to delay, inhibit, ameliorate and/or reduce the likelihood of symptomology of a patient with Wolfram Syndrome or heterozygous wolframin.

Disclosed is chemical compounds C that are derivatives of norbixin and have tropism for the eye, and are intended to be used in the treatment of eye diseases in mammals, in particular in the context of altering the retinal pigment epithelium and more particularly in the context of age-related macular degeneration (AMD) and Stargardt's disease.

This document provides AAVs and methods and materials for making and using AAVs. For example, AAVs containing a capsid polypeptide that includes an amino acid segment having a DPIVMIDNDKPIT sequence (or a variant thereof) are provided. This document also provides compositions containing an AAV described herein, nucleic acid molecules encoding an AAV described herein, conjugating polypeptides, nucleic acid molecules encoding a conjugating polypeptide described herein, and methods for making a composition that includes two or more different AAVs covalently linked together.

The disclosure provides a dual-vector intein-mediated protein trans-splicing system, cells, compositions, and methods of using the same for gene therapy. In some embodiments, the disclosure provides methods and compositions for treating an autosomal recessive type of non-syndromic deafness, DFNB16, by delivering a STRC gene, encoding a STRC protein, using the dual-vector system described herein.

The disclosure provides a dual-vector intein-mediated protein trans-splicing system, cells, compositions, and methods of using the same for gene therapy. In some embodiments, the disclosure provides methods and compositions for treating an autosomal recessive type of non-syndromic deafness, DFNB16, by delivering a STRC gene, encoding a STRC protein, using the dual-vector system described herein.

The disclosure provides polynucleotides containing inner hair cell-specific promoters, as well as vectors containing the same, that can be used to promote expression of a transgene specifically in inner hair cells. The polynucleotides described herein may be operably linked to a transgene, such as a transgene encoding a therapeutic protein, so as to promote inner hair cell-specific expression of the transgene. The polynucleotides described herein may be operably linked to a therapeutic transgene and used for the treatment of subjects having or at risk of developing hearing loss.

The disclosure provides polynucleotides containing inner hair cell-specific promoters, as well as vectors containing the same, that can be used to promote expression of a transgene specifically in inner hair cells. The polynucleotides described herein may be operably linked to a transgene, such as a transgene encoding a therapeutic protein, so as to promote inner hair cell-specific expression of the transgene. The polynucleotides described herein may be operably linked to a therapeutic transgene and used for the treatment of subjects having or at risk of developing hearing loss.

Polynucleotides encoding peptides, proteins, enzymes, and functional fragments thereof are disclosed. The polynucleotides of the disclosure can be effectively delivered to an organ, such as the lung, and expressed within cells of the organ. The polyribonucleotides of the disclosure can be used to treat a disease or condition associated with a gene of the ATP-binding cassette (ABC) family, such as ABCA3.