[Expression of marker genes in muscle fibers after transfection in vivo, mediated by lactoferrin].
The capacity of milk iron-transporting human protein lactoferrin (LF) to deliver genetic constructions into cells was studied in an effort to correct hereditary defects. The purified LF and LF conjugates containing either polylysine (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 the marker genes was tested immunochemically. Mice were transfected with either pDMD1 plasmid carrying a full-size cDNA for human dystrophin gene or pCMVLacZ plasmid carrying the gene of bacterial beta-galactosidase. The marker gene expression was detected in the muscular fibers. The dystrophin-positive 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 limbs. beta-Galactosidase activity was revealed only in the injected muscles. The highest amount of DPMF (9%) was recorded in mice who received the complex of DNA with nonmodified LF. Specific LF-mediated human transfection as a means of stimulating the receptor-mediated endocytosis of genetic constructions and addressed gene transfer to human muscles are discussed.
Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, Russia.
N I
NI
Sinogeeva
M A
MA
Bogdanova
T D
TD
Aleĭnikova
M M
MM
Shavlovskiĭ
V S
VS
Gaĭtskhoki
O V
OV
Ostapenko
P B
PB
Glazkov
V S
VS
Baranov
D000818:Animals; D004587:Electrophoresis, Agar Gel; D005819:Genetic Markers; D006801:Humans; D007781:Lactoferrin / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D010957:Plasmids; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics
D005819:Genetic Markers; D001616:beta-Galactosidase; D007781:Lactoferrin