Table 1.
VCN, chimerism and IDS activity after lentiviral gene therapy
| Transgene (C-Terminal Tagging) | Linker | Tag | VCN Per Diploid Genome in Bone Marrow (PSI/Albumin) | Chimerism in Bone Marrow (CD45.1+ CD45.2−) | IDS Activity in Bone Marrow (nmol/mg × 4 h) | IDS Activity in Plasma (nmol/mg × 4 h) | n |
|---|---|---|---|---|---|---|---|
| IDSco | N/A | N/A | 2.351 ± 1.329 | 91.103 ± 2.577 | 5,215.7 ± 1,160.4 | 130.09 ± 34.51 | 6 |
| IDS.IGF2co | (LGGGGS)x4 | AA 1, 8–67 hIGF2 | 2.953 ± 1.132 | 81.167 ± 18.104 | 4,344.4 ± 1,353.8 | 66.83 ± 15.66 | 6 |
| IDS.ApoE2co | (LGGGGS)x4 | AA (141–149)x2 hApoE | 2.595 ± 1.694 | 84.585 ± 7.347 | 3,504.4 ± 1,952.4 | 133.76 ± 54.62 | 10 |
| IDS.RAP12x2co | (LGGGGS)x4 | AA (151–262) Gly (151–262) hRAP | 1.982 ± 1.613 | 81.954 ± 19.196 | 2,893.2 ± 2,187.4 | 107.68 ± 53.46 | 7 |
| GFP | N/A | N/A | 0.610 ± 0.261 | N/A | 9.5 ± 8.5 | 0.31 ± 0.02 | 6 |
| Ids y/− untreated | N/A | N/A | 0.004 ± 0.001 | 4.4975 ± 3.282 | 11.6 ± 4.9 | 0.51 ± 0.37 | 6 |
| WT untreated | N/A | N/A | 0.003 ± 0.000 | 6.0701 ± 2.678 | 40.5 ± 32.8 | 1.92 ± 0.22 | 6 |
Gene therapy-treated mice were irradiated with an irradiation dose of 9 Gray and transplanted with 106 hematopoietic stem and progenitor cells transduced at a multiplicity of infection of 1.
Chimerism for the GFP group could not be measured due to the overlap of the GFP and FITC excitation spectra (see Materials and Methods).
AA, amino acid; ApoE, Apolipoprotein E; co, codon optimized; GFP, green fluorescent protein; h, human; IDS, iduronate 2-sulfatase; IGF2, insulin-like growth factor; LGGGGS, lysine–glycine–glycine–glycine–glycine–serine; N/A, not applicable; RAP, receptor-associated protein; PSI, lentiviral packaging signal; VCN, vector copy number per diploid genome; WT, wild type.