IN-VIVO GENE-TRANSFER INTO RABBIT THYROID FOLLICULAR CELLS BY DIRECT DNA INJECTION

Direct injection of DNA expression vectors into muscle leads to expres sion of encoded recombinant gene products in mature muscle cells. This phenomenon is not shared by most other organs. We have surveyed vario us organs in the rabbit to identify other cell types that would expres s DNA vectors after direct injection. We observed that thyroid follicu lar cells were capable of acquiring plasmid DNA and expressing recombi nant gene products after direct interstitial injection of plasmid vect ors into the thyroid gland. The level of expression of a chloramphenic ol acetyltransferase (CAT) reporter gene in thyroid tissue was similar to that seen in muscle tissue three days after injection in controlle d experiments. Using a beta-galactosidase reporter gene, expression wa s localized to thyroid follicular cells. CAT activity decreased with f irst-order kinetics and a half-life t(1/2) of 40 hr. DNA was identifie d in thyroid tissue by polymerase chain reaction (PCR) analysis and di splayed first-order elimination kinetics with a half-life t(1/2) of 10 hr. The persistence of the gene and gene product in the thyroid was s ignificantly different from that observed after injection of DNA vecto rs into muscle os delivery of DNA vectors to the liver using asialogly coprotein/polylysine/DNA complexes, suggesting that there are signific ant differences in the process of DNA uptake or compartmentalization i n these experimental systems. These results introduce the possibility of developing the thyroid as a novel target for treating certain thyro id or systemic diseases using DNA vectors.