Massachusetts Institute of Technology

Albert Einstein College of Medicine

Philippe LeBoulch

Irving M London

Karen Westerman

Dorothy Y Tuan

Eric Bouhassira

Ken Julian Takekoshi

Gene therapy methods and compositions for high level expression of anti-sickling globin proteins in erythroid cells for treating Sickle Cell disease are described.

Compositions and methods for treating sickle cell disease

Methods and compositions for transforming cells, resulting in efficient and stable site-specific integration of transgenes, are disclosed. Transformation is achieved by introducing into a cell an acceptor vector, preferably a retroviral vector, which integrates into the genome of the cell. The acceptor vector comprises two incompatible lox sequences, L1 and L2. A donor vector is then introduced into the cell comprising a transgene flanked by the same L1 and L2 sequences. Stable gene transfer is initiated by contacting the lox L1 and L2 sequences with Cre recombinase.

Methods and compositions for transforming cells

A process and means for the design and the optimization of retroviral vectors transducing human .beta.-globin gene and .beta.-Locus Control Region (.beta.-LCR) derivatives, hereafter referred to as [.beta.-globin/LCR] retroviruses, which successfully meet the following criteria required for gene therapy applications: (1) stability of proviral transmission (low frequency of rearrangements similar to retroviral vectors considered stable in the art) upon infection of cell-lines and murine bone marrow cells, (2) improved viral titer, thereby allowing successful infection of bone marrow cells, and (3) high erythroid expression of the transduced human .beta.-globin gene, are described, along with specific constructs.

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Cambridge, MA, United States of America

Philippe LeBoulch