Figure 2.
Consistent, therapeutic, γ-globin expression of the mLARβΔγV5 lentiviral vector in β-thalassemic mice. (A) Cellulose acetate Hb electrophoresis gels were used to separate the different Hb species in red cell lysates from mice that underwent transplantation with β-thalassemic BM cells transduced with the indicated vectors. This β-thalassemic mouse strain has the “diffuse” Hb pattern characterized by an uppermost \(\mathrm{m}{\alpha}_{2}\mathrm{m}{\beta}_{2}^{\mathrm{minor}}\)
species and a faster migrating \(\mathrm{m}{\alpha}_{2}{\beta}_{2}^{\mathrm{maj}}\)
species. Chimeric mα2hγ2 molecules (termed HbF, indicated by the solid horizontal arrow) migrate faster than the endogenous murine Hb species. No endogenous murine “single” Hb molecules, which migrate between the “diffuse” and chimeric species, were observed, indicating full donor engraftment. The left panel shows samples from mice that underwent transplantation with BM cells transduced with the d432βΔγm vector, whereas the right panel shows samples from mice that underwent transplantation with mLARβΔγV5-transduced cells. Percent F equals the quantity of the chimeric mα2hγ2 species, estimated by densitometry, as a proportion of all Hb species. Vector copy number (VC no.) is the average copy number in PBLs as estimated by DNA PCR. The percent F per VC is the mean output of chimeric mα2hγ2 molecules per average vector copy number. (B) Mean Hb concentration (± standard error of the mean [SEM]) of mice that underwent transplantation with mock-transduced β-thalassemic BM cells, β-thalassemic BM transduced with the indicated γ-globin vectors, or mock-transduced wild-type (WT) BM cells. The mean Hb concentration improvement per vector copy is indicated where applicable. *Statistically significant difference in mean Hb value of mLARβΔγV5 mice versus d432βΔγm mice, P = .029, one-sided.
![Figure 2. Consistent, therapeutic, γ-globin expression of the mLARβΔγV5 lentiviral vector in β-thalassemic mice. (A) Cellulose acetate Hb electrophoresis gels were used to separate the different Hb species in red cell lysates from mice that underwent transplantation with β-thalassemic BM cells transduced with the indicated vectors. This β-thalassemic mouse strain has the “diffuse” Hb pattern characterized by an uppermost \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{m}{\alpha}_{2}\mathrm{m}{\beta}_{2}^{\mathrm{minor}}\) \end{document} species and a faster migrating \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{m}{\alpha}_{2}{\beta}_{2}^{\mathrm{maj}}\) \end{document} species. Chimeric mα2hγ2 molecules (termed HbF, indicated by the solid horizontal arrow) migrate faster than the endogenous murine Hb species. No endogenous murine “single” Hb molecules, which migrate between the “diffuse” and chimeric species, were observed, indicating full donor engraftment. The left panel shows samples from mice that underwent transplantation with BM cells transduced with the d432βΔγm vector, whereas the right panel shows samples from mice that underwent transplantation with mLARβΔγV5-transduced cells. Percent F equals the quantity of the chimeric mα2hγ2 species, estimated by densitometry, as a proportion of all Hb species. Vector copy number (VC no.) is the average copy number in PBLs as estimated by DNA PCR. The percent F per VC is the mean output of chimeric mα2hγ2 molecules per average vector copy number. (B) Mean Hb concentration (± standard error of the mean [SEM]) of mice that underwent transplantation with mock-transduced β-thalassemic BM cells, β-thalassemic BM transduced with the indicated γ-globin vectors, or mock-transduced wild-type (WT) BM cells. The mean Hb concentration improvement per vector copy is indicated where applicable. *Statistically significant difference in mean Hb value of mLARβΔγV5 mice versus d432βΔγm mice, P = .029, one-sided.](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/104/8/10.1182_blood-2004-03-0863/6/zh80200468190002.jpeg?Expires=1722437374&Signature=hXOSRPesXbKMLWxZSKqkVF0uf-VgSw~U3QdT1ueI0GIc-~2GPMUrpg~jbiWZgcbHO7ZL5Tgr~sSs1xtkFsvXVxJ5RqpmDMPQ35iis7wbVHNdT7yxyniGGs30ZcGFpqiwJYa9ZkuRMRm~9rnmlBFfOIOZ6pjHhBk0K0ivAFuZUQw4JeNk3cxFwZ0H6TcU7QOIEFZym4z8DJPpwlvGI2wjt2TI157tix68xa99ahajUOzUHrld6fItw42nmpLM8NH-BNT-D1QvGHnS3bQurU7XTV5bafB2L46sAm1u4Zfj39xTHSCWLNQ~8iBksHVz~6bgHy-M4zy08rFZX3PtHaUcYA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
