| First Author | Dorin JR | Year | 1996 |
| Journal | Gene Ther | Volume | 3 |
| Issue | 9 | Pages | 797-801 |
| PubMed ID | 8875228 | Mgi Jnum | J:36166 |
| Mgi Id | MGI:83604 | Citation | Dorin JR, et al. (1996) A demonstration using mouse models that successful gene therapy for cystic fibrosis requires only partial gene correction. Gene Ther 3(9):797-801 |
| abstractText | Quantifying the level of transgene expression necessary for phenotypic effect is an important consideration in designing somatic gene therapy protocols. A nonlinear relationship between phenotype and gene activity is predicted by control analysis for any autosomal recessive condition. The unaffected phenotype of heterozygotes for autosomal recessive disorders demonstrates that 50% of the normal level of gene expression is sufficient to prevent disease. By extension, an exaggerated and positive effect on the mutant phenotype is predicted to arise from only a small addition of normal transgene expression delivered by gene therapy. We tested this expectation directly by intercrossing mice carrying different Cftr alleles which modulate Cftr gene expression from 0 to 100%. We demonstrate that 5% of the normal level of Cftr gene expression results in a disproportionately large correction of the chloride ion transport defect (50% of normal) and essentially complete rescue of the intestinal disease (100% survival). If follows that even modest levels of transgene expression and only partial correction of CFTR channel activity may have a significant clinical impact. |
