Abstract: Disclosed are recombinant virions that have a capsid protein, or a variant thereof, of a protoparvovirus or tetraparvovirus, and a nucleic acid that includes a heterologous nucleic acid.

Abstract: The present disclosure relates to a pharmaceutical composition for the treatment of Leber congenital amaurosis, and a method for treating Leber congenital amaurosis using the pharmaceutical composition.

Abstract: The application describes ceDNA vectors having linear and continuous structure for delivery and expression of a transgene. ceDNA vectors comprise an expression cassette flanked by two ITR sequences, where the expression cassette encodes a transgene encoding FIX protein. Some ceDNA vectors further comprise cis-regulatory elements, including regulatory switches. Further provided herein are methods and cell lines for reliable gene expression of FIX protein in vitro, ex vivo and in vivo using the ceDNA vectors. Provided herein are method and compositions comprising ceDNA vectors useful for the expression of FIX protein in a cell, tissue or subject, and methods of treatment of diseases with said ceDNA vectors expressing FIX protein. Such FIX protein can be expressed for treating disease, e.g., hemophilia B.

Abstract: This disclosure provides methods and pharmaceutical compositions for attenuating immune response in a subject suffering from a genetic disorder and receiving gene or nucleic acid therapy. The pharmaceutical compositions and formulations may include immunosuppressants, such as protein kinase inhibitors, including tyrosine kinase inhibitors (TKIs), in conjunction with various types of therapeutic nucleic acids (TNAs) and carriers (e.g., lipid nanoparticles).