Effective gene transfer into central nervous system following ultrasound-microbubbles-induced opening of the blood-brain barrier.
To investigate whether ultrasound-targeted microbubble destruction (UTMD) could transfer gene into central nervous system (CNS) following blood-brain barrier disruption (BBBD), DNA-loaded microbubbles were infused into the mice intravenously following ultrasonic exposure. Opening of the BBB, changes of mRNA and expression of enhanced green fluorescent protein (EGFP), and safety evaluation were measured. By UTMD, EGFP were substantially expressed in the cytoplasm of the neurons at the sonicated area with minor erythrocytes extravasation and the mRNA and expression of EGFP were markedly enhanced by about 15-fold and 10-fold, respectively, than that with US alone (p < 0.01). No EGFP was detected in the mice treated with DNA-loaded microbubbles or plasmid alone. The gene expression reached a climax at 48 h, gradually reduced to a much lower level thereafter. These results demonstrated UTMD could effectively enhance exogenous gene delivery and expression in CNS following BBBD, and this technique may provide a new method for CNS gene therapy.
Department of Neurosurgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Qin
Q
Huang
Jinmu
J
Deng
Zongyi
Z
Xie
Feng
F
Wang
Song
S
Chen
Bo
B
Lei
Peng
P
Liao
Ning
N
Huang
Zhibiao
Z
Wang
Zhigang
Z
Wang
Yuan
Y
Cheng
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology* / Q000528:radiation effects*; D004247:DNA / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D045423:Microbubbles; D013010:Sonication / Q000379:methods*; D014162:Transfection / Q000379:methods*
D004247:DNA