Introduction of the human growth hormone gene into the guinea pig mammary gland by in vivo transfection promotes sustained expression of human growthhormone in the milk throughout lactation

We tested the feasibility of transfecting mammary tissue in vivo with an ex pression plasmid encoding the human growth hormone (hGH) gene, under the co ntrol of the cytomegalovirus promoter. Guinea pig mammary glands were trans fected with plasmid DNA infused through the nipple canal and expression was monitored in control and transfected glands by radioimmanoassay of milk sa mples for hGH. Sustained expression of hGH throughout lactation was attaine d with a polyion transfection complex shown to be optimal for the transfect ion of bovine mammary cells, in vitro. However, contrary to expectations, h GH expression was consistently 5- to 10-fold higher when DEAE-dextran was u sed alone for transfection. Thus polyion complexes which are optimal for th e transfection of cells in vitro may not be optimal in vivo. The highest co ncentrations of hGH in milk were obtained when glands were transfected with in 3 days before parturition. This method may have application for studying the biological role or physical properties of recombinant proteins express ed in low quantities, or for investigating the regulation of gene promoters without the need to construct viral vectors or produce transgenic animals. (C) 2000 Elsevier Science B.V. All rights reserved.