Viral vectors for prophylaxis and therapy of hemoglobinopathies

A method for inducing expression of human beta-globin in erythrocytes for use in prophylaxis and/or therapy of a hemoglobinopathy in an individual comprising introducing into erythrocyte progenitor cells a polynucleotide encoding:

• i) a 5′ long terminal repeat (LTR) and a self-inactivating 3′ LTR;
• ii) at least one polyadenylation signal;
• iii) at least one promoter;
• iv) a globin gene locus control region (LCR);
• v) an ankyrin insulator element (Ank);
• vi) a Woodchuck Post-Regulatory Element (WPRE) configured such that the WPRE does not integrate into a target genome;
• and
• vii) a sequence that is a reverse complement of a sequence encoding modified human beta-globin comprising a βT87Q mutation (B-globinM), wherein the sequence encoding the B-globinM comprises a first intron (intron 1) between exon 1 and exon 2, and a second intron (intron 2) between exon 2 and exon 3 of said B-globinM sequence, wherein intron 2 comprises more than 476 nucleotides of human B-globinM intron 2 sequence;
• wherein, subsequent to the introducing, the erythrocyte progenitor cells differentiate into erythrocytes, wherein the erythrocytes are present in the individual and the erythrocytes produce more human beta-globin than a control.