Adipose tissue as a novel target for in vivo gene transfer by adeno-associated viral vectors.
Traditionally, skeletal muscle and liver are the preferred target organs for gene transfer to supply a transgene product into the systemic circulation. In this respect, adipose tissue presents a number of attractive features. However, adipose tissue transduction in vivo has not been feasible by conventional methods. To solve this issue, we tested the utility of excipients in adeno-associated virus (AAV) vector-mediated gene transfer and found that Pluronics are suitable for this purpose. In a histological analysis of adipose tissue in db/db mice, Pluronic F88 showed the greatest augmentative effect on beta-galactosidase expression in combination with the AAV1 vector. When the vector encoding mouse erythropoietin (Epo) was used in the same manner, increased plasma Epo concentrations were observed (230 +/- 80 versus 58 +/- 14 mU/ml). Moreover, the plasma Epo concentration returned to the normal level after the surgical removal of transduced adipose tissue. No damage was observed in the transduced tissue. Our results indicate that the proposed method is safe and efficient for gene transfer into adipose tissues, thus providing an alternative for supplemental gene therapy.
Mizukami
Hiroaki
H
Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan. miz@jichi.ac.jp
Mimuro
Jun
J
Ogura
Tsuyoshi
T
Okada
Takashi
T
Urabe
Masashi
M
Kume
Akihiro
A
Sakata
Yoichi
Y
Ozawa
Keiya
K
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D000229:Dependovirus / Q000235:genetics*; D004921:Erythropoietin / Q000032:analysis; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D019076:Transgenes; D001616:beta-Galactosidase / Q000235:genetics
D017931:DNA Primers; D004921:Erythropoietin; D001616:beta-Galactosidase