Abstract: The present invention relates to engineered liver-specific enhancers, synthetic promoters containing the enhancers, expression vectors containing the synthetic promoters, as well as methods of using the enhancer or the expression vector thereof to address the need in the field, such as treatment of various genetic diseases or conditions associated with the liver. In some embodiments, the engineered enhancer comprises one or more DNA binding sites for transcription factors.

Abstract: Described herein are novel engineered peptides, viral vectors, and pharmaceutical compositions thereof, and uses of the same for increasing ?-GAL A expression and for the treatment of conditions associated with ?-GAL A deficiency, such as Fabry disease.

Abstract: The present invention relates to an engineered human factor VIII polypeptide, which includes at least two substituted amino acids in A1 domain of hFVIII. In some embodiments, the substituted amino acids comprise L50V and L152P. In some embodiments, the substituted amino acids further comprise one or more of amino acid substitutions selected from the group consisting of D20S, G22L, I61T, D115E, F129I, G132D, Q139E, and L159F. The present invention also relates to engineered hFVIII polypeptide encoding nucleic acid fragment, an expression vector or a rAAV vector contains such nucleic acid fragment, and a method of using engineered hFVIII polypeptide to treat hemophilia A patients.

Abstract: In one aspect, present invention provides a recombinant mutant human factor VIII having increased expression and/or secretion as compared to wild-type factor VIII. In certain embodiments, the recombinant factor VIII includes one or more amino acid substitution(s) selected from the group consisting of 186, Y105, A108, D115, Q117, F129, G132, H134, M147 and L152. In other aspects, the present invention provides FVIII encoding nucleic acids, FVIII-expression vectors, as well as methods of using the modified FVIII genes in the treatment of FVIII deficiencies, such as hemophilia A.

Abstract: In one aspect, present invention provides a recombinant mutant human factor VIII having increased expression and/or secretion as compared to wild-type factor VIII. In certain embodiments, the recombinant factor VIII includes one or more amino acid substitution(s) selected from the group consisting of I86, Y105, A108, D115, Q117, F129, G132, H134, M147 and L152. In other aspects, the present invention provides FVIII encoding nucleic acids, FVIII-expression vectors, as well as methods of using the modified FVIII genes in the treatment of FVIII deficiencies, such as hemophilia A.

Abstract: In one aspect, present invention provides a recombinant mutant human factor VIII having increased expression and/or secretion as compared to wild-type factor VIII. In certain embodiments, the recombinant factor VIII includes one or more amino acid substitution(s) selected from the group consisting of I86, Y105, A108, D115, Q117, F129, G132, H134, M147 and L152. In other aspects, the present invention provides FVIII encoding nucleic acids, FVIII-expression vectors, as well as methods of using the modified FVIII genes in the treatment of FVIII deficiencies, such as hemophilia A.