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公开(公告)号:US20230045199A1
公开(公告)日:2023-02-09
申请号:US17786147
申请日:2020-12-23
发明人: Gerd BLOBEL , Scott PESLAK , Junwei SHI
IPC分类号: C12N15/113 , A61P7/06 , A61K31/454 , A61K31/713
摘要: Methods and compositions for producing fetal hemoglobin and treating a hemoglobinopathy or thalassemia are disclosed.
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公开(公告)号:US20180008725A1
公开(公告)日:2018-01-11
申请号:US15545159
申请日:2016-01-21
发明人: Stefano RIVELLA , Laura BREDA , Alisa DONG , Gerd BLOBEL , Wulan DENG
IPC分类号: A61K48/00 , C12N15/867
CPC分类号: A61K48/005 , C12N15/86 , C12N15/867 , C12N2740/15043 , C12N2830/40 , C12N2830/48 , C12N2830/50 , C12N2830/52
摘要: 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.
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