Dual vector for inhibition of human immunodeficiency virus
AssigneesCSL Behring Gene Therapy, Inc., The Regents of the University of California
InventorsIrvin CHEN, Dong Sung AN, Michelle MILLINGTON, Maureen BOYD, Geoffrey P. SYMONDS, Louis Randall BRETON
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Abstract
The present invention provides an expression vector for preventing or inhibiting HIV entry, fusion or replication in mammalian cells. In particular, the invention provides a recombinant retroviral vector that encodes an inhibitor of a HIV co-receptor, such as CCR5 or CXCR4, and a protein that inhibits HIV fusion to target cells and/or HIV replication. Pharmaceutical compositions comprising such constructs and methods of use thereof to prevent or treat HIV infection in a patient are also disclosed.
Claims16
1-24. (canceled)
A method of treating or preventing HIV infection in a patient, comprising administering a pharmaceutical composition to the patient, the pharmaceutical composition comprising (i) an expression vector comprising a first nucleic acid sequence encoding a shRNA having the sequence of SEQ ID NO:
- 1, wherein the first nucleic acid sequence is operably linked to an H1 promoter, and a second nucleic acid sequence encoding a C46 protein that inhibits HIV fusion to a target cell, wherein the second nucleic acid sequence is operably linked to a UbiquitinC pol II promoter;
- and (ii) a pharmaceutically acceptable carrier,
- wherein following administration of the pharmaceutical composition, the immune system of the patient is at least partially reconstituted with HIV-resistant cells.
A method of treating or preventing HIV infection in a patient, comprising:
- (i) transducing hematopoietic cells with an expression vector, the expression vector comprising a first nucleic acid sequence encoding a shRNA having the sequence of SEQ ID NO:
- 1, wherein the first nucleic acid sequence is operably linked to an H1 promoter, and a second nucleic acid sequence encoding a C46 protein, wherein the second nucleic acid sequence is operably linked to a UbiquitinC pol II promoter, and
- (ii) transplanting said transduced hematopoietic cells in the patient, wherein said transduced hematopoietic cells are resistant to HIV infection.
A method of treating or preventing HIV infection in a human patient, comprising:
- (i) transducing hematopoietic cells with a lentiviral expression vector, the lentiviral expression vector comprising:
- a first nucleic acid sequence encoding a shRNA having the sequence of SEQ ID NO:
- 1, wherein the first nucleic acid sequence is operably linked to an H1 promoter;
- and a second nucleic acid sequence encoding a C46 protein that inhibits HIV fusion to a target cell, wherein the second nucleic acid sequence is operably linked to a UbiquitinC pol II promoter;
- and
- (ii) transplanting the transduced hematopoietic cells in the patient, the transduced hematopoietic cells having at least 30% less CCR5 receptors as compared with nontransduced cells and wherein the transduced hematopoietic cells express the C46 protein;
- and
- wherein the transduced hematopoietic cells reconstitute the immune system of the patient such that the transplanted transduced hematopoietic cells provide a continual source of at least one of granulocytes, monocytes/macrophages, or lymphocytes that are resistant to HIV infection.
Dependencies are inferred from the claim text.