Clonal gene therapy: transplanted mouse fibroblast clones express human α1-antitrypsin gene in vivo

RI Garver Jr, A Chytil, M Courtney, RG Crystal - Science, 1987 - science.org
RI Garver Jr, A Chytil, M Courtney, RG Crystal
Science, 1987science.org
A retroviral vector was used to insert human α1-antitrypsin (α1AT) complementary DNA into
the genome of mouse fibroblasts to create a clonal population of mouse fibroblasts secreting
human α1AT. After demonstrating that this clone of fibroblasts produced α1AT after more
than 100 population doublings in the absence of selection pressure, the clone was
transplanted into the peritoneal cavities of nude mice. When the animals were evaluated 4
weeks later, human α1AT was detected in both sera and the epithelial surface of the lungs …
A retroviral vector was used to insert human α1-antitrypsin (α1AT) complementary DNA into the genome of mouse fibroblasts to create a clonal population of mouse fibroblasts secreting human α1AT. After demonstrating that this clone of fibroblasts produced α1AT after more than 100 population doublings in the absence of selection pressure, the clone was transplanted into the peritoneal cavities of nude mice. When the animals were evaluated 4 weeks later, human α1AT was detected in both sera and the epithelial surface of the lungs. The transplanted clone of fibroblasts could be recovered from the peritoneal cavities of those mice and demonstrated to still be producing human α1AT. Thus, even after removal of selective pressure, a single clone of retroviral vector-infected cells that expressed an exogenous gene in vitro, continued to do so in vivo, and when recovered, continued to produce the product of the exogenous gene.
AAAS