Intrabiliary infusion of naked DNA vectors targets periportal hepatocytes in mice

Deplazes, Sereina; Schlegel, Andrea; Song, Zhuolun; Allegri, Gabriella; Rimann, Nicole; Scherer, Tanja; Willimann, Melanie; Opitz, Lennart; Cunningham, Sharon C; Alexander, Ian E; Kipar, Anja; Häberle, Johannes; Thöny, Beat; Grisch-Chan, Hiu Man

doi:10.1016/j.omtm.2022.10.006

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Deplazes, S., Schlegel, A., Song, Z., Allegri, G., Rimann, N., Scherer, T., Willimann, M., Opitz, L., Cunningham, S. C., Alexander, I. E., Kipar, A., Häberle, J., Thöny, B., & Grisch-Chan, H. M. (2022). Intrabiliary infusion of naked DNA vectors targets periportal hepatocytes in mice. Molecular Therapy - Methods & Clinical Development, 27, 352–367. https://doi.org/10.1016/j.omtm.2022.10.006

Abstract

Hydrodynamic tail vein injection (HTV) is the "gold standard" for delivering naked DNA vectors to mouse liver, thereby transfecting predominately perivenous hepatocytes. While HTV corrects metabolic liver defects such as phenylketonuria or cystathionine β-synthase deficiency, correction of spf ash mice with ornithine transcarbamylase (OTC) deficiency was not possible despite overexpression in the liver, as the OTC enzyme is primarily expressed in periportal hepatocytes. To target periportal hepatocytes, we established hydrodynamic ret