Therapeutic retroviral vectors for gene therapy
Assigneebluebird bio, Inc.
InventorsPhilippe Leboulch, Robert Pawliuk, Karen Westerman
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Abstract
The invention provides improved compositions and methods for achieving gene therapy in hematopoietic cells and hematopoietic precursor cells, including erythrocytes, erythroid progenitors, and embryonic stem cells. The invention further provides 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.
Claims17
A self-inactivating (SIN) Human Immunodeficiency Virus (HIV) vector comprising:
- a) a 5′ HIV LTR;
- b) a hepatitis B virus post-transcriptional regulatory element (PRE) or an HIV reverse response element (RRE);
- c) a lentiviral central polypurine tract/DNA flap (cPPT/FLAP);
- c) a β-globin promoter;
- d) a β-globin locus control region (LCR);
- and
- e) a 3′ HIV LTR comprising:
- i) at least one deletion compared to the wild type 3′ HIV LTR;
- and
- ii) an insulator element comprising the nucleotide sequence set forth in SEQ. ID No.:
- 2
- wherein the β-globin promoter and β-globin LCR within the SIN vector are operatively linked to a gene of interest.
A self-inactivating (SIN) Human Immunodeficiency Virus (HIV) vector comprising:
- a) a 5′ HIV LTR;
- b) an HIV reverse response element (RRE);
- c) an HIV central polypurine tract/DNA flap (cPPT/FLAP);
- d) a human β-globin promoter;
- e) a human β-globin locus control region (LCR) comprising the DNAase I hypersensitive sites 2, 3 and 4;
- f) a human β-globin 3′ enhancer;
- and
- g) a 3′ HIV LTR comprising:
- i) an insulator element comprising the nucleotide sequence set forth SEQ. ID No.:
- 2;
- and
- ii) a poly (A) sequence comprising the nucleotide sequence set forth in SEQ. ID No.:
- 1,
- wherein the human β-globin promoter, human β-globin LCR and human β-globin 3′ enhancer within the SIN vector are operatively linked to a gene of interest.
Dependencies are inferred from the claim text.