Immune tolerance induction to viral capsids

The method of claim 25, wherein therapeutic nucleic acid encodes an antigen, a therapeutic protein, or a therapeutic RNA.

The method of claim 36, wherein the second promoter comprises the nucleic acid sequence pf SEQ ID NO:

• 3, or a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO:
• 3.

A gene therapy vector comprising a nucleic acid sequence encoding an immunogenic portion of a capsid protein of an rAAV, wherein the nucleic acid sequence is operably linked to a promoter, and wherein the gene therapy vector is capable of delivering the nucleic acid sequence to liver cell or HSC and expressing the at least a portion of the capsid protein of the therapeutic rAAV in the liver or HSC, thereby inducing immune tolerance to the therapeutic rAAV.

A method for delivering a therapeutic nucleic acid to in a subject comprising

• (a) administering to the subject an effective amount of a therapeutic recombinant adeno-associated virus (rAAV) comprising a first nucleic acid comprising the therapeutic nucleic acid operably linked to a first promoter;
• and
• (b) administering to the subject an effective amount of a HSC expressing at least a portion of a capsid protein of the therapeutic rAAV, thereby inducing immune tolerance to the therapeutic rAAV.

A method of inducing immune tolerance to a therapeutic recombinant adeno-associated virus (rAAV) in a subject comprising:

• administering to the subject an effective amount of a HSC expressing at least a portion of a capsid protein of the therapeutic rAAV, thereby inducing immune tolerance to the therapeutic rAAV.