Gene suture--a novel method for intramuscular gene transfer and its application in hypertension therapy.
In this report, reporter gene beta-galactosidase (LacZ) was chosen to compare two different intramuscular gene transfer methods, direct injection and gene suture. Evidence showed that gene suture can produce a higher foreign gene express efficiency in skeletal muscle compared with the direct injection method. The highly efficient eukaryotic expressing vectors of human atrial natriuretic factor (ANF) were constructed (pcD2/pAdVAntage/hANF and pcDNA3/hANF), and in vivo ANF gene delivery was performed by intramuscular gene suture. The effects of ANF gene transfer on blood pressure and renal sodium and water excretion were studied in three models of hypertensive animals. Results showed that a marked decrease of mean arterial pressure (MAP) and a significant increase of urine volume and urinary sodium excretion was produced in rats receiving the hANF construct due to the local expression of ANF and its secretion into plasma. Taken together, these results indicate that gene suture may represent a novel gene delivery modality in gene therapy.
Qin
Y J
YJ
Institute of Cardiovascular Basic Research, Beijing Medical University, PR China.
Zhang
J F
JF
Wei
Y J
YJ
Ding
J F
JF
Chen
K H
KH
Tang
J
J
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001794:Blood Pressure; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000628:therapy*; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D007763:Lac Operon / Q000235:genetics*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000652:urine; D001616:beta-Galactosidase / Q000235:genetics
D009320:Atrial Natriuretic Factor; D004247:DNA; D012964:Sodium; D001616:beta-Galactosidase