Modified factor ix, and compositions, methods and uses for gene transfer to cells, organs, and tissues

A method of treating a human subject with severe or moderate hemophilia B comprising:

• administering to said subject a therapeutically effective amount of a recombinant adeno-associated virus (rAAV) vector comprising a vector genome encapsidated by an AAV capsid,
• wherein said vector genome comprises at least two AAV inverted terminal repeats (ITR), an expression control element conferring liver tissue-specific expression operably linked with a nucleic acid sequence encoding human Factor IX (FIX) protein, and a polyadenylation signal sequence, wherein said nucleic acid sequence encoding human FIX protein is at least 70% identical to SEQ ID NO:10, has a reduced number of CpG di-nucleotides compared to wild-type nucleic acid sequence encoding human FIX protein and encodes the same human FIX protein encoded by SEQ ID NO:10,
• wherein said therapeutically effective amount of said rAAV vector is a dose of at least 5×1011 vector genomes per kilogram (vg/kg) subject body weight, and is effective to reduce the severe or moderate hemophilia B to mild hemophilia B or a hemophilia B disease-free state.