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• W2044698963 abstract "Small DNA fragments (SDFs) including normal M and α1-antitrypsin deficiency (α1-ATD) Z sequences were generated and transfected into peripheral blood monocytes from M subjects and Z α1-ATD patients. Untreated M and α1-ATD monocytes secreted 32 ± 1.1 and 23 ± 1.4 ng of α1-AT per 106 monocytes over 24 hr. After tumor necrosis factor (TNF)-α stimulation, the α1-AT secretion from M monocytes increased significantly to 50 ± 2.1 ng/106 over 24 hr (p = 0.0004), whereas there was no change in secreted α1-AT from TNF-α-stimulated α1-ATD monocytes. However, after Z SDF transfection, M monocytes failed to increase α1-AT secretion in response to TNF-α stimulation. Transfecting α1-ATD monocytes with the M SDF resulted in a significant increase in α1-AT secretion (p = 0.03) after TNF-α stimulation to 55 ± 2.7 ng/106 cells. Monocytes from a further 13 α1-ATD patients constitutively produced α1-AT after the first 24 hr. Transfection with either transfection reagent alone or with Z SDF slightly increased α1-AT secretion over the subsequent 24 hr. However, M SDF transfection significantly increased α1-AT secretion further, compared with untreated or sham transfection. Untreated, transfection reagent-treated, and Z SDF-transfected α1-ATD monocytes generated polymerase chain reaction products from Z primers. M SDF-treated α1-ATD monocytes generated bands with M primers, indicating the generation of a corrected transcript. In conclusion, the defective gene can be corrected in α1-ATD monocytes with SDFs, and treatment is associated with an increase in α1-AT secretion. The development of this methodology to repair the gene defect in hepatocytes should have beneficial effects on secretion, thereby protecting both the lung and liver." @default.
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• W2044698963 date "2007-11-01" @default.
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• W2044698963 title "Modification of Gene Expression and Increase in<i>α</i>₁-Antitrypsin (<i>α</i>₁-AT) Secretion After Homologous Recombination in<i>α</i>₁-AT-Deficient Monocytes" @default.
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• W2044698963 doi "https://doi.org/10.1089/hum.2007.073" @default.
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