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Stem Cell Related Patent Number US5760012
| Title: | Methods and compounds for curing diseases caused by mutations | | Inventors: | Kmiec, Eric B.; Malvern, PA, USA
Cole-Strauss, Allyson; Philadelphia, PA, USA
Yoon, Kyonggeun; Berwyn, PA, USA | | Summary: | Described herein are chimeric nucleic acid repair vectors, methods and uses thereof. The invention relates to a nucleic acid characterized by not more than one 3' end and one 5' end which comprise a segment of unpaired bases configured in such a manner that the unpaired bases separate the nucleic acid into a first strand and a second strand, such that first and second strands comprise a first region and a second region, respectively, with each region having at least 15 nucleotides. Further disclosed are properties by which each nucleotide of the first region is Watson-Crick paired to a nucleotide of the second region such that the first region comprises at least 8 ribonucleotides having other than a 2'-hydroxyl moiety, which are Watson-Crick paired to 2'-deoxynucleotides such that the ribonucleotides form at least one ribonucleotide segment of at least 3 ribonucleotides by which the sequence of the first or the second region is the sequence of a fragment of a wild-type allele of a human gene. Therapeutic applications are included for the treatment of diseases such as sickle cell anemia, beta-thalassemia, Gaucher disease, hypercholesterolemia, emphysema and hemophilia. | | Abstract: | 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. | | US Patent Website: | Click Here for Full Text of Patent | | Title Number: | US5760012 | | Application Number: | US1996000640517 | | Date Filed: | 01/05/1996 | | Date Published: | 02/06/1998 | | Assignee: | Thomas Jefferson University, Philadelphia, PA, USA |
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