Hepatic injection of a lentivirus carrying the Hfe gene is effective in preventing HH. (A) Schematic representations of the lentiviral vectors THW and TGW. The various components shown are the long terminal repeat (LTR), self-inactivating long terminal repeat (SIN-LTR), the HIV rev-response and central polypurine tract elements (RRE, cPPT), the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE), the liver-specific TTR promoter (TTR), the GFP, and the mouse Hfe gene (Hfe). (B) Representative fluorescence analyses of liver sections from animals 2 months after being transduced with PBS or TGW. Liver was fixed in 4% paraformaldehyde and frozen in OCT embedding medium. Images were captured on a Nikon TE2000-U inverted microscope equipped with DIC, a CoolSnap cf digital camera (Photometrics), and a Plan fluor objective 20×/0.45 (Nikon), and acquired using IP Lab Version 3.6.5a software (Scanalytics). Brightness/contrast and color balance were adjusted using Adobe Photoshop Version 7.0.1 (Adobe Systems). (C) Expression of Hfe and Hamp in the livers of mice injected with lentivirus. (D) Serum iron, (E) Tf saturation, and (F) organ iron content of mice injected with THW together with the appropriate controls. Data are mean ± SEM of 5 or 6 individual age- and sex-matched mice. *P ≤ .05. **P ≤ .01. ***P ≤ .001.