Abstract: Methods and compositions for improved gene therapy are disclosed.

Abstract: In one aspect of the instant invention, lentiviral vectors are provided, particularly for treating hemoglobinopathies. Composition comprising the lentiviral vector are also encompassed by the instant invention. In accordance with another aspect of the instant invention, methods of inhibiting, treating, and/or preventing a hemoglobinopathy (e.g., sickle cell disease or thalassemia) in a subject are provided. In a particular embodiment, the method comprises administering a viral vector of the instant invention to a subject in need thereof hemoglobinopathy. In a particular embodiment, the subject has sickle cell anemia.

Abstract: A heating device for an exhaust system of an internal combustion engine and having: a tubular body, where a combustion chamber is obtained on the inside; a fuel injector, which injects fuel into the combustion chamber; at least one inlet opening, which can be connected to a fan so as to receive an air flow, which is directed to the combustion chamber and gets mixed with the fuel; a feeding channel, which receives air from the inlet opening, surrounds an end portion of the fuel injector and ends with a nozzle, which is arranged around an injection point of the fuel injector; and a spark plug, which is mounted through a side wall of the tubular body so as to trigger the combustion of a mixture of air and fuel. The fuel injector is configured to spray at least 80% of the fuel against an inner surface of the feeding channel.

Abstract: Methods and compositions for producing heme and treating sideroblastic anemia are disclosed.

Abstract: Provided are compositions and methods for inducing expression of human beta-globin in erythrocytes for use in prophylaxis and/or therapy of a hemoglobinopathy in an individual. The method generally entails introducing into CD34+ cells a polynucleotide encoding: i) a 5? long terminal repeat (LTR) and a self-inactivating 3? LTR; ii) at least one polyadenylation signal; iii) at least one promoter; iv) a globin gene locus control region (LCR); v) an ankyrin insulator element (Ank); vi) a Woodchuck Post-Regulatory Element (WPRE) configured such that the WPRE does not integrate into a target genome; and vii) a sequence that is a reverse complement of a sequence encoding human beta-globin, and can include beta-globin that has a ?T87Q mutation. Intron 2 of the beta globin gene can be a complete intron. Modified erythrocyte progenitor cells, recombinant vectors and virions comprising recombinant polynucleotides, and methods of making the vectors and virions are included.

Abstract: A heating device for an exhaust system of an internal combustion engine and having: a tubular body, where a combustion chamber is obtained on the inside; a fuel injector, which injects fuel into the combustion chamber; at least one inlet opening, which can be connected to a fan so as to receive an air flow, which is directed to the combustion chamber and gets mixed with the fuel; a feeding channel, which receives air from the inlet opening, surrounds an end portion of the fuel injector and ends with a nozzle, which is arranged around an injection point of the fuel injector; and a spark plug, which is mounted through a side wall of the tubular body so as to trigger the combustion of a mixture of air and fuel. The fuel injector is configured to spray at least 80% of the fuel against an inner surface of the feeding channel.

Abstract: Provided are compositions and methods for inducing expression of human beta-globin in erythrocytes for use in prophylaxis and/or therapy of a hemoglobinopathy in an individual. The method generally entails introducing into CD34+ cells a poly-nucleotide encoding: i) a 5? long terminal repeat (LTR) and a self-inactivating 3? LTR; ii) at least one polyadenylation signal; iii) at least one promoter; iv) a globin gene locus control region (LCR); v) an ankyrin insulator element (Ank); vi) a Woodchuck Post-Regulatory Element (WPRE) configured such that the WPRE does not integrate into a target genome; and vii) a sequence that is a reverse complement of a sequence encoding human beta-globin, and can include beta-globin that has a PT87Q mutation. Intron 2 of the beta globin gene can be a complete intron. Modified erythrocyte progenitor cells, recombinant vectors and virions comprising recombinant polynucleotides, and methods of making the vectors and virions are included.

Abstract: A heating device for an exhaust system of an internal combustion engine; the heating device has: a first tubular body wherein a combustion chamber is obtained; a fuel injector to inject fuel into the combustion chamber; an inlet opening, which is obtained through the first tubular body and can be connected to a fan to receive an air flow, which is directed into the combustion chamber; a hot air outlet opening to let hot air out of the combustion chamber; an outlet duct, which originates from the outlet opening; a spark plug which is mounted through a side wall of the first tubular body to trigger the combustion of a mixture of air and fuel; and a labyrinth, which surrounds a side wall of the tubular body, starts from the inlet opening, ends in the combustion chamber, and the air must necessarily flow out of the inlet opening until reaching the combustion chamber.

Abstract: The present invention provides methods, agents, compounds, and compositions useful for administering to subjects having or at risk of having anemias. In certain embodiments, methods herein comprise administering two agents to a subject, which are useful for the treatment of an anemia.

Abstract: Methods and compositions for producing hemoglobin and treating alpha-thalassemia are disclosed.

Abstract: Provided are compositions and methods for inducing expression of human beta-globin in erythrocytes for use in prophylaxis and/or therapy of a hemoglobinopathy in an individual. The method generally entails introducing into CD34+ cells a polynucleotide encoding: i) a 5? long terminal repeat (LTR) and a self-inactivating 3? LTR; ii) at least one polyadenylation signal; iii) at least one promoter; iv) a globin gene locus control region (LCR); v) an ankyrin insulator element (Ank); vi) a Woodchuck Post-Regulatory Element (WPRE) configured such that the WPRE does not integrate into a target genome; and vii) a sequence that is a reverse complement of a sequence encoding human beta-globin, and can include beta-globin that has a PT87Q mutation. Intron 2 of the beta globin gene can be a complete intron. Modified erythrocyte progenitor cells, recombinant vectors and virions comprising recombinant polynucleotides, and methods of making the vectors and virions are included.

Abstract: Recombinant lentiviral vectors having a region encoding a functional ?-globin gene; and large portions of the ?-globin locus control regions which include DNase I hypersensitive sites HS2, HS3 and HS4 provides expression of ?-globin when introduced into a mammal, for example a human, in vivo. Optionally, the vector further includes a region encoding a dihydrofolate reductase. The vector may be used in treatment of hemoglobinopathies, including ?-thalessemia and sickle-cell disease. For example, hematopoietic progenitor or stem cells may be transformed ex vivo and then restored to the patient. Selection processes may be used to increase the percentage of transformed cells in the returned population. For example, a selection marker which makes transformed cells more drug resistant than untransformed cells allows selection by treatment of the cells with the corresponding drug.

Abstract: Recombinant lentiviral vectors having a region encoding a functional ?-globin gene; and large portions of the ?-globin locus control regions which include DNase I hypersensitive sites HS2, HS3 and HS4 provides expression of ?-globin when introduced into a mammal, for example a human, in vivo. Optionally, the vector further includes a region encoding a dihydrofolate reductase. The vector may be used in treatment of hemoglobinopathies, including ?-thalessemia and sickle-cell disease. For example, hematopoietic progenitor or stem cells may be transformed ex vivo and then restored to the patient. Selection processes may be used to increase the percentage of transformed cells in the returned population. For example, a selection marker which makes transformed cells more drug resistant than untransformed cells allows selection by treatment of the cells with the corresponding drug.

Abstract: Recombinant lentiviral vectors having a region encoding a functional ?-globin gene; and large portions of the ?-globin locus control regions which include DNase I hypersensitive sites HS2, HS3 and HS4 provides expression of ?-globin when introduced into a mammal, for example a human, in vivo. Optionally, the vector further includes a region encoding a dihydrofolate reductase. The vector may be used in treatment of hemoglobinopathies, including ?-thalessemia and sickle-cell disease. For example, hematopoietic progenitor or stem cells may be transformed ex vivo and then restored to the patient. Selection processes may be used to increase the percentage of transformed cells in the returned population. For example, a selection marker which makes transformed cells more drug resistant than un-transformed cells allows selection by treatment of the cells with the corresponding drug.

Abstract: Recombinant lentiviral vectors having a region encoding a functional &bgr;-globin gene; and large portions of the &bgr;-globin locus control regions which include DNase I hypersensitive sites HS2, HS3 and HS4 provides expression of &bgr;-globin when introduced into a mammal, for example a human, in vivo. Optionally, the vector further includes a region encoding a dihydrofolate reductase. The vector may be used in treatment of hemoglobinopathies, including &bgr;-thalessemia and sickle-cell disease. For example, hematopoietic progenitor or stem cells may be transformed ex vivo and then restored to the patient. Selection processes may be used to increase the percentage of transformed cells in the returned population. For example, a selection marker which makes transformed cells more drug resistant than un-transformed cells allows selection by treatment of the cells with the corresponding drug.