Thomas Jefferson University

Kyonggeun Yoon

Eric B Kmiec

Allyson D Cole-Strauss

The invention concerns the use of duplex oligonucleotides having both 2'-deoxyribonucleotides and ribonucleotides, wherein there is base pairing between the two types of nucleotides. The sequence of the oligonucleotide is selected so that the 3' and 5' most regions of the oligonucleotide are homologous with (identical to) the sequence of a preselected target gene of a cell. The two regions of homology embrace a region that is heterologous with the target sequence. The introduction of the oligonucleotide into the nucleus of the cell causes the alteration of the target gene such that the sequence of the altered target gene is the sequence of the heterologous region. Consequently, the oligonucleotides of the invention are termed Chimeric Repair Vectors (CRV). In one embodiment of the invention the target gene is a globin gene and the target cell is a hematopoietic stem cell. This embodiment can be used to correct certain hemoglobinopathies such as Sickle Cell Disease, .beta.-thalassemia, and also Gaucher Disease. The rate of correction of the globin gene is high enough so that no selection of the treated hematopoietic stem cells is required to obtain a therapeutically significant effect. In one embodiment the ribose moieties of the nucleotides of the CRV contain methylated 2'-oxygens.

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Berwyn, PA, United States of America

Kyonggeun Yoon