Abstract: The present invention provides recombinant adeno-associated virus (rAAV) vectors comprising a heterologous nucleotide sequence encoding factor VIII (factor VIII). In preferred embodiments, the factor VIII is a B-domain deleted factor VIII. Also provided are methods of producing a high titer stock of the inventive rAAV/factor VIII vectors. Another aspect of the invention is a method of delivering a nucleotide sequence encoding factor VIII to a cell, preferably for subsequent administration to a subject. The present invention further provides methods of administering rAAV/factor VIII to a subject, e.g., for the treatment of hemophilia. The rAAV vector may be administered by any route, but is preferably administered to the liver.

Abstract: The subject invention concerns a recombinant adeno-associated virus vector characterized as being capable of delivering and expressing at least one mammalian gene into a genome of a mammalian host cell such that the expression of the gene is regulated in a tissue specific manner by cis-acting regulatory and promoter elements of the gene. A method of using this recombinant adeno-associated virus vector for therapeutic purposes is also provided.

Abstract: The molecules and methods of the present invention provide a means for in vivo production of a trans-spliced molecule in a selected subset of cells. The pre-trans-splicing molecules of the invention are substrates for a trans-splicing reaction between the pre-trans-splicing molecules and a pre-mRNA which is uniquely expressed in the specific target cells. The in vivo trans-splicing reaction provides a novel mRNA which is functional as mRNA or encodes a protein to be expressed in the target cells. The expression product of the mRNA is a protein of therapeutic value to the cell or host organism a toxin which causes killing of the specific cells or a novel protein not normally present in such cells. The invention further provides PTMs that have been genetically engineered for the identification of exon/intron boundaries of pre-mRNA molecules using an exon tagging method.

Abstract: The present invention provides recombinant adeno-associated virus (rAAV) vectors comprising a heterologous nucleotide sequence encoding factor VIII (factor VIII). In preferred embodiments, the factor VIII is a B-domain deleted factor VIII. Also provided are methods of producing a high titer stock of the inventive rAAV/factor VIII vectors. Another aspect of the invention is a method of delivering a nucleotide sequence encoding factor VIII to a cell, preferably for subsequent administration to a subject. The present invention further provides methods of administering rAAV/factor VIII to a subject, e.g., for the treatment of hemophilia. The rAAV vector may be administered by any route, but is preferably administered to the liver.

Abstract: The subject invention concerns a recombinant adeno-associated virus vector characterized as being capable of delivering and expressing at least one mammalian gene into a genome of a mammalian host cell such that the expression of the gene is regulated in a tissue specific manner by cis-acting regulatory and promoter elements of the gene. A method of using this recombinant adeno-associated virus vector for therapeutic purposes is also provided.