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 FVIII 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 FVIII protein in vitro, ex vivo and in vivo using the ceDNA vectors. Provided herein are methods and compositions comprising ceDNA vectors useful for the expression of FVIII protein in a cell, tissue or subject, and methods of treatment of diseases with said ceDNA vectors expressing FVIII protein. Such FVIII protein can be expressed for treating disease, e.g., hemophilia A.

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).

Abstract: Provided herein are lipid formulations comprising a lipid and a capsid free, non-viral vector (e.g. ceDNA). Lipid particles (e.g., lipid nanoparticles) of the invention include a lipid formulation that can be used to deliver a capsid-free, non-viral DNA vector to a target site of interest (e.g., cell, tissue, organ, and the like).

Abstract: Provided herein are methods and constructs related to minimizing immune responses using modified dexamethasone compounds when administering a desired transgene in a cell achieved by delivery of the transgene with one or more doses of a ceDNA construct.

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 FVIII 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 FVIII 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 FVIII protein in a cell, tissue or subject, and methods of treatment of diseases with said ceDNA vectors expressing FVIII protein. Such FVIII protein can be expressed for treating disease, e.g., hemophilia A.

Abstract: Disclosed herein are HTT repressors and methods and compositions for use of these HTT repressors. Disclosed herein are methods and compositions for diagnosing, preventing and/or treating Huntington's Disease. In particular, provided herein are methods and compositions for modifying (e.g., modulating expression of) an HD HTT allele so as to prevent or treat Huntington Disease, including mHTT repressors (that repress mHTT transcripts and thus also repress mHTT protein expression).

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. Some ceDNA vectors further comprise cis-regulatory elements, including regulatory switches. Further provided herein are methods and cell lines for reliable gene expression 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 an antibody or fusion protein in a cell, tissue or subject. Such antibodies or fusion proteins can be expressed for treating disease or alternatively, for the production of antibodies or fusion proteins in a commercial setting.