Abstract
BackgroundGene 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 FindingsHere, 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/SignificanceThese results suggest that axonal transport is critical for gene transduction. Our study may provide a basis for developing therapeutic methods for efficient gene delivery into hard tissues.
Highlights
IntroductionThe ability to promote osteogenesis in a controlled way would be beneficial for the treatment of bone fractures and large segmental bone defects, for the fixation of artificial joints and for avoiding nonunion or delayed union of fractures [1]
Defective bone healing is a major clinical problem
To test the hypothesis that genes transfer to bone tissue via complicated networks between bone and the nervous system, we evaluated the efficacy of gene expression in the interior of bone via axonal transport following intramuscular injection of a nonviral vector [HVJ envelope]
Summary
The ability to promote osteogenesis in a controlled way would be beneficial for the treatment of bone fractures and large segmental bone defects, for the fixation of artificial joints and for avoiding nonunion or delayed union of fractures [1]. When therapeutic genes, such as bone morphogenetic protein (BMP) cDNAs, are supplied to bone fractures and bone defects, they can offer sustained delivery of proteins to a local area. In the case of hard tissues, such as bone, local gene delivery remains problematic owing to anatomical accessibility limitations of the target sites
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