Therapeutic retroviral vectors for gene therapy
Assigneesbluebird bio, Inc., Massachusetts Institute of Technology
InventorsPhilippe Louis LEBOULCH, Robert PAWLIUK, Karen WESTERMAN
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Abstract
Provided are improved compositions and methods for achieving gene therapy in hematopoietic cells and hematopoietic precursor cells, including erythrocytes, erythroid progenitors, and embryonic stem cells. Also provided are improved gene therapy methods for treating hematopoietic-related disorders. Retroviral gene therapy vectors that are optimized for erythroid specific expression and treatment of hemoglobinopathic conditions are disclosed.
Claims21
-21. (canceled)
A hematopoietic stem cell comprising a self-inactivating (SIN) lentiviral vector comprising:
- a) a human immunodeficiency virus 1 (HIV-1) 5′ long terminal repeat (LTR), wherein the promoter of the HIV-1 5′ LTR is replaced with a heterologous promoter;
- b) an RNA export element;
- c) a central polypurine tract or DNA FLAP (cPPT/FLAP);
- d) a human β-globin promoter;
- e) a human β-globin locus control region (LCR), wherein the β-globin promoter and β-globin LCR are operatively linked to a polynucleotide encoding a human globin;
- f) a human β-globin 3′ enhancer element;
- and
- g) a HIV-1 3′ LTR, wherein the 3′ LTR comprises at least one deletion compared to the wild-type HIV-1 3′ LTR.
A hematopoietic progenitor cell comprising a self-inactivating (SIN) lentiviral vector comprising:
- a) a human immunodeficiency virus 1 (HIV-1) 5′ long terminal repeat (LTR), wherein the promoter of the HIV-1 5′ LTR is replaced with a heterologous promoter;
- b) an RNA export element;
- c) a central polypurine tract or DNA FLAP (cPPT/FLAP);
- d) a human β-globin promoter;
- e) a human β-globin locus control region (LCR), wherein the β-globin promoter and β-globin LCR are operatively linked to a polynucleotide encoding a human globin;
- f) a human β-globin 3′ enhancer element;
- and
- g) a HIV-1 3′ LTR, wherein the 3′ LTR comprises at least one deletion compared to the wild-type HIV-1 3′ LTR.
Dependencies are inferred from the claim text.