Efficient liposome-mediated gene transfection and expression in the intacthuman uterus

Although gene therapy has been used for correction of metabolic defects in diseases such as cystic fibrosis, as adjuvant treatment in cancer, and in t he treatment of infectious diseases, there has been no report of gene trans fer to the intact female reproductive tract. We assessed the ability to tra nsfect the human uterus ex vivo and thereby evaluate the applicability of g ene therapy to gynecology. The uterine lumen was accessed transcervically, using an intrauterine insemination catheter. pcDNA3.1 plasmid containing th e Escherichia coli lacZ reporter gene was delivered to each uterus via lipo some-mediated transfection. Control uteri were transfected with empty pcDNA 3.1. Immunohistochemical analysis revealed beta -galactosidase expression i n the lacZ-treated uteri in endometrial epithelial cells, endometrial strom al cells, and myometrium to a depth of 1.75 em from the endometrial-myometr ial junction. Highest expression was seen in endometrial glandular epitheli al cells, with significant expression in the stroma and adjacent myometrium . Each of these cell types in the control uteri showed no beta -galactosida se expression. Successful gene transfection and expression in the intact hu man uterus can be accomplished easily, rapidly, and efficiently. Gene thera py may have wide applicability in the treatment and study of gynecologic di sease.