Lentiviral Vectors Having a Mutated Integrase Protein and uses Thereof

A vector genome for the preparation of a lentiviral vector, wherein the vector genome encodes a lentiviral vector expressing an integrase protein comprising at least one point mutation that is a substitution of an aspartic acid residue at position 167 by an amino acid selected from the group consisting of histidine, arginine and lysine.

A method for obtaining a lentiviral vector expressing an integrase protein comprising at least one point mutation that is a substitution of an aspartic acid residue at position 167 by an amino acid selected from the group consisting of histidine, arginine and lysine, comprising

• transfecting in vitro a permissive cell with a plasmid containing a lentiviral vector genome encoding the lentiviral vector, and at least one other plasmid providing, in trans, gag, pol and env sequences encoding GAG, POL and envelope polypeptides, or encoding a portion of the GAG, POL and envelope polypeptides sufficient to enable formation of retroviral particles, and
• harvesting the lentiviral vector.

A method for expressing a transgene in a mammalian cell, comprising

• transducing the mammalian cell with a lentiviral vector comprising the transgene, wherein the lentiviral vector expresses an integrase protein comprising at least one point mutation that is a substitution of an aspartic acid residue at position 167 by an amino acid selected from the group consisting of histidine, arginine and lysine.

A method of performing gene therapy in a subject in need thereof, comprising

• delivering a gene of interest to the subject by administering to the subject a lentiviral vector that expresses the gene of interest, wherein the lentiviral vector expresses an integrase protein comprising at least one point mutation that is a substitution of an aspartic acid residue at position 167 by an amino acid selected from the group consisting of histidine, arginine and lysine.

A method for eliciting an immune response to an antigenic polypeptide in a subject in need thereof, comprising

• administering to the subject a lentiviral vector comprising a transgene encoding the antigenic polypeptide, wherein the lentiviral vector expresses an integrase protein comprising at least one point mutation that is a substitution of an aspartic acid residue at position 167 by an amino acid selected from the group consisting of histidine, arginine and lysine, and wherein the antigenic polypeptide is expressed from said transgene in the subject so as to elicit an immune response to the antigenic polypeptide.

A method for the treatment of a disease selected from the group consisting of cancer, autoimmune disease, ocular disorders, blood disorders, neurological disorders, lung disorders, and infectious diseases in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a lentiviral vector comprising a transgene that expresses an agent that treats the disease, wherein the lentiviral vector expresses an integrase protein comprising at least one point mutation that is a substitution of an aspartic acid residue at position 167 by an amino acid selected from the group consisting of histidine, arginine and lysine.