US 11,753,654 B2
Globin gene therapy for treating hemoglobinopathies
Michel Sadelain, New York, NY (US); and Annalisa Cabriolu, Villacidro (IT)
Assigned to MEMORIAL SLOAN-KETTERING CANCER CENTER, New York, NY (US)
Filed by MEMORIAL SLOAN-KETTERING CANCER CENTER, New York, NY (US)
Filed on Jun. 2, 2020, as Appl. No. 16/890,436.
Application 16/890,436 is a continuation of application No. PCT/US2018/064256, filed on Dec. 6, 2018.
Claims priority of provisional application 62/595,277, filed on Dec. 6, 2017.
Prior Publication US 2020/0291433 A1, Sep. 17, 2020
Int. Cl. C12N 15/86 (2006.01); A61P 7/00 (2006.01); C12N 9/22 (2006.01)
CPC C12N 15/86 (2013.01) [A61P 7/00 (2018.01); C12N 9/22 (2013.01); C12N 2310/20 (2017.05); C12N 2830/008 (2013.01); C12N 2830/15 (2013.01); C12N 2830/30 (2013.01)] 14 Claims
 
1. An expression cassette comprising a globin gene or a functional portion thereof operably linked to a β-globin locus control region (LCR) that comprises a Dnase I hypersensitive site-2 (HS2) region, a Dnase I hypersensitive site-3 (HS3) region, and a Dnase I hypersensitive site-4 (HS4) region, wherein the HS4 region has a length of less than about 800 bp and does not comprise the nucleotide sequence set forth in SEQ ID NO: 50, and wherein the β-globin LCR comprises:
(a) a HS2 region consisting of nucleotides 45-860 of SEQ ID NO: 9, a HS3 region consisting of the nucleotide sequence set forth in SEQ ID NO: 5, and a HS4 region consisting of nucleotides 115-868 of SEQ ID NO: 6;
(b) a HS2 region consisting of the nucleotide sequence set forth in SEQ ID NO: 33, a HS3 region consisting of the nucleotide sequence set forth in SEQ ID NO: 34, and a HS4 region consisting of the nucleotide sequence set forth in SEQ ID NO: 35;
(c) a HS1 region consisting of the nucleotide sequence set forth in SEQ ID NO: 3, a HS2 region consisting of nucleotides 45-860 of SEQ ID NO: 9, a HS3 region consisting of the nucleotide sequence set forth in SEQ ID NO: 5, and a HS4 region consisting of nucleotides 115-868 of SEQ ID NO: 6; or
(d) a HS1 region consisting of the nucleotide sequence set forth in SEQ ID NO: 3, a HS2 region consisting of the nucleotide sequence set forth in SEQ ID NO: 33, a HS3 region consisting of the nucleotide sequence set forth in SEQ ID NO: 34, and a HS4 region consisting of the nucleotide sequence set forth in SEQ ID NO: 35.