axonal-transport-mediated gene transduction in the interior of rat boneaxonal-transport-mediated基因转导的室内鼠骨.pdf

Axonal-Transport-Mediated Gene Transduction in the Interior of Rat Bone 1 2 1 1 1 Toshitaka Okabayashi *, Kuniaki Nakanishi , Toyokazu Tsuchihara , Hiroshi Arino , Yasuo Yoshihara , 3 4 4 5 1 Susumu Tominaga , Maki Uenoyama , Shinya Suzuki , Masataka Asagiri , Koichi Nemoto 1 Department of Orthopaedic Surgery, National Defense Medical College, Saitama, Japan, 2 Department of Laboratory Medicine, National Defense Medical College Hospital, Saitama, Japan, 3 Department of Pathology and Laboratory Medicine, National Defense Medical College, Saitama, Japan, 4 Division of Environmental Medicine, National Defense Medical College Research Institute, Saitama, Japan, 5 Department of Chemistry and Biochemistry, University of California San Diego, San Diego, California, United States of America Abstract Background: Gene transduction has been considered advantageous for the sustained delivery of proteins to specific target tissues. However, in the case of hard tissues, such as bone, local gene delivery remains problematic owing to anatomical accessibility limitations of the target sites. Methodology/Principal Findings: Here, we evaluated the feasibility of exogenous gene transduction in the interior of bone via axonal transport following intramuscular administration of a nonviral vector. A high expression level of the transduced gene was achieved in the tibia ipsilateral to the injected tibialis anterior muscle, as well as in the ipsilateral sciatic nerve and dorsal root ganglia. In sciatic transection rats, the gene expression level was significantly lowered in bone. Conclusions/Signi