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Mitigation of radiation‐induced skin injury by AAV2‐mediated MnSOD gene therapy
Author(s) -
Yan Shiqing,
Brown Stephen L.,
Kolozsvary Andrew,
Freytag Svend O.,
Lu Mei,
Kim Jae Ho
Publication year - 2008
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1226
Subject(s) - genetic enhancement , reactive oxygen species , in vivo , ionizing radiation , green fluorescent protein , subcutaneous injection , cancer research , medicine , chemistry , immunology , microbiology and biotechnology , biology , gene , irradiation , biochemistry , nuclear physics , physics
Background Radiation‐induced, long‐lived free radicals, reactive oxygen species and pro‐inflammatory cytokines have been implicated in the resultant tissue injury after exposure to ionizing radiation. Methods An approach designed to reduce the damaging effects of reactive oxidants employs metalloenzymes of superoxide dismutase (SOD), such as MnSOD. Recombinant adeno‐associated virus 2 (AAV2) provides safe and long‐term expression in humans. We tested the effectiveness of AAV2‐MnSOD‐hrGFP, a vector expressing MnSOD and green fluorescent protein (GFP) in preclinical models. Results Infection of cultured cells with AAV2‐MnSOD‐hrGFP showed enhanced expression of MnSOD and GFP. Sustained expression of GFP was achieved for at least 1 month in vivo following administration of AAV2‐MnSOD‐hrGFP to subcutaneous tissue of C57BL/6J mice. A single subcutaneous injection of AAV2‐MnSOD‐hrGFP significantly mitigated acute skin injury following single dose of irradiation of either 30 or 35 Gy. Conclusions The proof‐of‐concept demonstrated in the present study together with the known safety profile in humans indicate that AAV‐mediated MnSOD expression has potential countermeasure utility against normal tissue injury following radiation therapy or radiological accident. Copyright © 2008 John Wiley & Sons, Ltd.