Optimized lentiviral vector compromising minimal enhancer elements for stem cell gene therapy of hemoglobinopathies

A recombinant lentiviral vector (LV) comprising:

• an expression cassette comprising a nucleic acid construct comprising:
• (a) a human β-globin locus control region (LCR) sequence selected from the group consisting of:
• (i) a sequence consisting of reduced length HS sequences set forth in SEQ ID NO:
• 2, SEQ ID NO:
• 3, SEQ ID NO:
• 4, SEQ ID NO:
• 5, SEQ ID NO:
• 6, SEQ ID NO:
• 7, SEQ ID NO:
• 8, SEQ ID NO:
• 9, and SEQ ID NO:
• 10;
• (ii) a sequence consisting of reduced length HS sequences set forth in SEQ ID NO:
• 12, SEQ ID NO:
• 13, SEQ ID NO:
• 14, SEQ ID NO:
• 15, SEQ ID NO:
• 16, SEQ ID NO:
• 17, SEQ ID NO:
• 18, SEQ ID NO:
• 19, and SEQ ID NO:
• 20;
• (iii) a sequence consisting of reduced length HS sequences set forth in SEQ ID NO:
• 22, SEQ ID NO:
• 23, SEQ ID NO:
• 24, SEQ ID NO:
• 25, SEQ ID NO:
• 26, SEQ ID NO:
• 27, SEQ ID NO:
• 28, and SEQ ID NO:
• 29;
• (iv) a sequence consisting of reduced length HS sequences set forth in SEQ ID NO:
• 31, SEQ ID NO:
• 32, SEQ ID NO:
• 33, SEQ ID NO:
• 34, SEQ ID NO:
• 35, and SEQ ID NO:
• 36;
• or
• (v) a sequence consisting of reduced length HS sequences set forth in SEQ ID NO:
• 38, SEQ ID NO:
• 39, SEQ ID NO:
• 40, SEQ ID NO:
• 41, and SEQ ID NO:
• 42;
• and
• (b) a heterologous gene to be expressed by said construct operably linked to said human β-globin LCR sequence;
• and
• wherein said LV is a TAT-independent and self-inactivating (SIN) lentiviral vector.