Granted Patent
B2
US 12,655,446 · App. 17/049,061 · Granted Jun 16, 2026
Compositions and methods for hemoglobin production
Inventors:
Stefano Rivella (Philadelphia, PA); Laura Breda (Philadelphia, PA); Alisa Dong (Glendale, CA); Silvia Pires Lourenco (Philadelphia, PA); Amaliris Gonzalez (Philadelphia, PA)
Assignee:
THE CHILDREN'S HOSPITAL OF PHILADELPHIA
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Abstract
In one aspect of the instant invention, lentiviral vectors are provided, particularly for treating hemoglobinopathies. Composition comprising the lentiviral vector are also encompassed by the instant invention. In accordance with another aspect of the instant invention, methods of inhibiting, treating, and/or preventing a hemoglobinopathy (e.g., sickle cell disease or thalassemia) in a subject are provided. In a particular embodiment, the method comprises administering a viral vector of the instant invention to a subject in need thereof hemoglobinopathy. In a particular embodiment, the subject has sickle cell anemia.
Claims (17)
1 . A lentiviral vector comprising a nucleic acid molecule comprising:
i) a 5′ long terminal repeat (LTR) and a 3′ LTR, wherein one of said LTRs is self-inactivating;
ii) at least one polyadenylation signal;
iii) at least one promoter;
iv) a globin gene locus control region (LCR), wherein said LCR comprises HS1, HS2, HS3, and HS4, wherein said LCR comprises the nucleotide sequence of nucleotides 6766-10641 of SEQ ID NO: 1;
v) an ankyrin insulator element (Ank);
vi) a Woodchuck Post-Regulatory Element (WPRE), wherein the WPRE is 3′ of the 3′LTR; and
vii) a sequence encoding human beta-globin.
2 . The lentiviral vector of claim 1 , wherein said 3′ LTR is 411 nucleotides in length.
3 . The lentiviral vector of claim 1 , further comprising a Rev response element (RRE).
4 . The lentiviral vector of claim 3 , wherein said RRE is located between the LCR and the 3′LTR.
5 . The lentiviral vector of claim 1 , wherein the lentiviral vector is present in CD34+ cells.
6 . The lentiviral vector of claim 5 , wherein the CD34+ cells have been isolated from an individual who has a hemoglobinopathy.
7 . A composition comprising the lentiviral vector of claim 1 and a pharmaceutically acceptable carrier.
8 . A composition comprising viral particles, wherein the viral particles comprise the lentiviral vector of claim 1 .
9 . A method for inducing expression of human beta-globin in erythrocytes comprising introducing into erythrocyte progenitor cells a lentiviral vector of claim 1 .
10 . A lentiviral vector comprising SEQ ID NO: 1.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 2, 2021
From: RIVELLA, STEFANO; BREDA, LAURA; DONG, ALISA; PIRES LOURENCO, SILVIA; GONZALEZ, AMALIRIS
To: THE CHILDREN'S HOSPITAL OF PHILADELPHIA
Reel/Frame 055109/0327 →
Continuity (2)
Provisional Application
62664788
· Apr 30, 2018
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