Stable and Selective Transgene Expression in the Mammary Epithelium via In Utero Gene Transfer

Fetal gene transfer represents a promising approach to achieve sustained transgene expression within the hormonally responsive mammary epithelium through transduction of mammary stem cells. We have previously demonstrated the ability to transduce a regenerative mammary epithelial stem cell population through early gestational intra-amniotic injection of lentiviral vector. We hypothesized that selective mammary expression could be achieved by the early gestational intra-amniotic injection of lentiviral vector through the use of a mammary-specific promoter. Because the regulatory activity of many proto-oncogenes complicates the production of transgenic animals, the ability to selectively modulate mammary gene expression in this manner might allow tissue-specific manipulation and study of genetic elements important in breast development and oncogenesis. Such selective expression also represents a critical first step toward the application of in utero gene transfer techniques to the correction of inherited breast cancers, which might eventually enable fetal gene therapy to correct an adult disease.