2020年5月
rAAV8 and rAAV9-mediated long-term muscle transduction with tacrolimus (FK506) in non-human primates
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
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- 巻
- 18
- 号
- 開始ページ
- 44
- 終了ページ
- 49
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.omtm.2020.05.012
- 出版者・発行元
- Elsevir
To establish an efficient, safe immunosuppressive regimen of AAV-mediated gene therapy for Duchenne muscular dystrophy (DMD), we evaluated the effect of tacrolimus (FK506) on skeletal muscle transduction with AAV8 and AAV9 vectors expressing the LacZ and microdystrophin (M3) genes labeled by FLAG. We utilized 3–4-year-old Macaca fascicularis, screened for neutralizing antibodies against AAV. Three days before AAV injection and throughout the experiment, 0.06 mg/kg tacrolimus was intravenously administered. A viral suspension of 1 × 1013 viral genomes/muscle was intramuscularly injected bilateraly at the tibialis anterior and biceps brachii muscles, which were biopsied at 8, 16, 24, and 42 weeks after injection. Without tacrolimus, AAV8- and AAV9-mediated LacZ expression disappeared 8 and 16 weeks after transduction, respectively. With tacrolimus, AAV8/9-mediated LacZ expression persisted for at least 42 weeks after injection. At 42 weeks after AAV8CMVLacZ and AAV9CMVLacZ injection, nearly 50% and 17% of muscle fibers were positive for β-galactosidase, respectively. AAV8/9-mediated M3-FLAG expression lasted for up to 42 weeks using tacrolimus. No significant generalized toxicity
- リンク情報
- ID情報
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- DOI : 10.1016/j.omtm.2020.05.012
- ISSN : 2329-0501
- PubMed ID : 32577431
- PubMed Central 記事ID : PMC7298335