ApoE gene delivery inhibits severe hypercholesterolemia in newborn ApoE-KO mice.
Apolipoprotein E, a key regulator in cholesterol-rich lipoprotein metabolism, is considered a strong candidate for treating hypercholesterolemia and cardiovascular disease. Inherited deficiency of this protein results in type III hyperlipoproteinemia in humans. ApoE-knockout mice, which develop spontaneous hypercholesterolemia, are an excellent model of human atherosclerosis. Here we investigated the therapeutic effects of a plasmid vector encoding human APOE3 sequence intramuscularly injected in hypercholesterolemic newborn mice at the ages of 5 and 14 days. We further explored the possibility of inducing tolerance in newborns when injected early. Our data show that direct i.m. naked DNA injection reduces severe hypercholesterolemia in newborn mice. Moreover, when naked DNA is administrated early, no immune response is generated against the human APOE, allowing repeated administrations. Neonatal therapies are important for the treatment of many genetic childhood diseases where early administration is required to prevent developmental damage. We propose the use of direct i.m. naked gene transfer in newborns to prevent long-term damages arising from hypercholesterolemic conditions.
Signori
Emanuela
E
Institute of Neurobiology and Molecular Medicine, CNR-ARTOV, 00133 Rome, Italy. emanuela.signori@artov.inmm.cnr.it
Rinaldi
Monica
M
Fioretti
Daniela
D
Iurescia
Sandra
S
Seripa
Davide
D
Perrone
Giuseppe
G
Norata
Giuseppe Danilo
GD
Catapano
Alberico Luigi
AL
Fazio
Vito Michele
VM
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies; D001057:Apolipoproteins E / Q000008:administration & dosage / Q000172:deficiency* / Q000235:genetics*; D050197:Atherosclerosis / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D018076:DNA, Complementary / Q000008:administration & dosage; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006937:Hypercholesterolemia / Q000235:genetics* / Q000517:prevention & control*; D007109:Immunity; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010957:Plasmids / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D000906:Antibodies; D001057:Apolipoproteins E; D018076:DNA, Complementary; D002784:Cholesterol