Expression of marker genes in muscular fibers after in vivo lactoferrin-mediated transfection

The capacity of milk iron-transporting human protein lactoferrin (LF) to de liver genetic constructions into cells was studied in an effort to correct hereditary defects. The purified LF and LF conjugates containing either pol ylysine (C-1) or both polylysine and ficoll (C-2) were bound to plasmid DNA . These complexes were injected into mouse muscles, and the expression of t he marker genes was tested immunochemically. Mice were transfected with eit her pDMD1 plasmid carrying a full-size cDNA for human dystrophin gene or pC MVLacZ plasmid carrying the gene of bacterial beta-galactosidase. The marke r gene expression was detected in the muscular fibers. The dystrophin-posit ive muscular fibers (DPMF) were revealed in mdx mice (a model of Duchenne's dystrophy) in the regions of administration and in muscles of the other li mbs. beta-Galactosidase activity was revealed only in the injected muscles. The highest amount of DPMF (9%) was recorded in mice who received the comp lex of DNA with nonmodified LF. Specific LF-mediated human transfection as a means of stimulating the receptor-mediated endocytosis of genetic constru ctions and addressed gene transfer to human muscles are discussed.