Efficient gene transfer from innervated muscle into rat peripheral and central nervous systems using a non-viral haemagglutinating virus of Japan (HVJ)-liposome method.
We evaluated the feasibility of gene delivery into the peripheral and central nervous systems via retrograde axonal transport following injection of a haemagglutinating virus of Japan (HVJ)-liposome-DNA complex vector into an innervated muscle. Transfection efficiency was assessed by measuring luciferase activity, and was compared statistically with that achieved using a liposome-DNA control vector. High luciferase activity was observed in the injected muscle, the ipsilateral sciatic nerve, and the ipsilateral dorsal root ganglia on day 1 after gene transfer. The spinal cord also showed luciferase activity, although this was lower than in the other tissues. However, no activity was observed in the contralateral sciatic nerve or the contralateral dorsal root ganglia. In addition, we performed gene transfer twice, with a 1-week interval, to evaluate the feasibility of repeated therapeutic gene delivery. Again, a high transfection efficiency was observed immediately, even after the second gene transfer, and transfection efficiency was significantly higher at each defined time-point using the HVJ-liposome complex vector than using a control vector. These results indicate that this method could be used for repeated therapeutic gene delivery into muscle, nerve, dorsal root ganglia, and possibly spinal cord, without the need for a surgical approach, making it well suited to clinical applications.
Kato
Naoki
N
Department of Orthopaedic Surgery, National Defense Medical College Research Institute, Saitama, Japan. grd1505@gr.ndmc.ac.jp
Nakanishi
Kuniaki
K
Nemoto
Koichi
K
Morishita
Ryuichi
R
Kaneda
Yasufumi
Y
Uenoyama
Maki
M
Ikeda
Tomosumi
T
Fujikawa
Kyosuke
K
D000818:Animals; D001370:Axonal Transport; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D005240:Feasibility Studies; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D015870:Gene Expression / Q000187:drug effects; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D008081:Liposomes; D008156:Luciferases / Q000235:genetics; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation* / Q000821:virology; D017933:Peripheral Nervous System / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D029082:Sendai virus / Q000235:genetics*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D008081:Liposomes; D008156:Luciferases; D001616:beta-Galactosidase