Vectors and compositions for treating hemoglobinopathies

A lentiviral vector genomic RNA comprising:

• (a) an HIV-1 strain NL4-3 5′ long terminal repeat (LTR) comprising an R region and a U5 region;
• (b) a Ψ packaging signal;
• (c) an HIV-1 strain NL4-3 central polypurine tract (cPPT)/FLAP element;
• (d) an HIV-1 strain HXB3 RRE RNA export element;
• (e) an HIV-1 strain NL4-3 env splice acceptor sequence;
• a human β-globin promoter operably linked to a polynucleotide encoding a shmiR that comprises an antisense sequence that hybridizes to a human BCL11A mRNA, wherein the shmiR comprises the sequence set forth in SEQ ID NO:
• 1;
• (g) a human β-globin LCR comprising a HS2 DNAse I hypersensitive site comprising about 638 nucleotides, and a HS3 DNAse I hypersensitive site comprising about 847 nucleotides;
• and (h) an HIV-1 strain NL4-3 3′ SIN LTR comprising a U3 region comprising a deletion and an R region.