LNP-mFas gene therapy suppresses ALPS phenotype in mice. (A-C) DOTAP-Chol (A) and mouse Fas-encoding plasmid (B) were formulated at a 1:1 molecular ratio to produce LNP-mFas. The LNP-mFas was analyzed by scanning electric microscope (C). (D) The Fas^lpr mice were treated with LNP control (n = 3) and DOTAP-Chol–encapsulated mFas-encoding plasmid (LNP-mFas, n = 3) once every 2 weeks for 2 times. Shown are LN image (left panel) and quantification of LN weight (right panel). Ruler in mm scale. (E) Lymph nodes were collected from the control (LNP) and LNP-mFas–treated mice as shown in panel D and analyzed by histology. Shown are hematoxylin and eosin–stained sections (magnification x1000). Left panel: arrow points to plasma cells and circle indicates immunoblasts. Right panel: arrows point to plasma cells aggregated and included Mott cells. (F) Lymph node cells as shown in panel D were stained with the indicated antibodies and analyzed by flow cytometry.