Naked cDNA encoding secreted proteins for intra-arterial and intramuscular gene transfer.
Experience with intra-arterial and intramuscular gene transfer of VEGF illustrates in prototypical fashion how features of the gene, protein, and target tissue may all contribute to phenotypic modulation of the host despite the low transfection efficiency typical of naked plasmid DNA. These features include the fact that VEGF is naturally secreted, binds to cell-surface heparan sulfates, is generated by hypoxic endothelial cells, reduces apoptosis, and binds to high-affinity receptors that are upregulated by hypoxia. Thus the success of gene therapy is not solely a function of vectors or transfection efficiency.
Asahara
T
T
Department of Medicine (Cardiology), St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135, USA.
Tsurumi
Y
Y
Takeshita
S
S
Isner
J M
JM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001157:Arterial Occlusive Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics*; D016228:Endothelial Growth Factors / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007269:Injections, Intra-Arterial; D007273:Injections, Intramuscular; D008222:Lymphokines / Q000235:genetics*; D010957:Plasmids; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors