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KMID : 0364820070430030151
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Korean Journal of Microbiology
2007 Volume.43 No. 3 p.151 ~ p.158
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Potential Reproductive Toxicity Study of p53 Expressing Adenoviral Vector in Mice
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Rhee Gyu-Seek
Kim Seung-Hee
Park Kui-Lea
Lee Rhee-Da
Kwack Seung-Jun
Chae Soo-Young
Kim Soon-Sun
Seok Ji-Hyun
Chung Soo-Youn
Lee Seung-Hoon
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Abstract
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The possibility of inadvertent introduction of therapeutic gene expressing viral vectors has raised safety concerns about germ-line infection. Particularly, for indications such as prostate cancer and ovarian cancer, the proximity of the point of viral administration to organs of the reproductive system raises concerns regarding inadvertent germ-line transmission of genes carried by the virus vector. To evaluate the safety of in vivo adenovirus mediated gene transfer, we explored the biodistribution, persistance and potential germ-line transmission of p53-expressing adenovirus (Ad-CMV-p53). Both male and female Balb/c mice were injected with 1 ×109 PFU of Ad-CMV-p53. The PCR analysis showed that there were detectable vector sequences in liver, kidney, spleen, seminal vesicle, epididymis, prostate, ovary, and uterus. The RT-PCR analysis for detecting inserted gene, p53 showed that Ad-CMV-p53 viral RNA were present in spleen, prostate and ovary. Direct injected male and female mice of adenovirus vector into testis and ovary were mated and their offspring were evaluated for germ-line transmission of the adenoviral vector. The PCR and RT-PCR analysis showed no evidence of germline transmission, although vector sequences were detected in DNA extracted from gonadal tissues. Real-time
PCR result confirmed a significant decrease of adenovirus in gonad tissues 1 week after injection. We have also
analysed the cell specific localization of viral DNA in gonad tissues by using in-situ PCR. Positive signals were
detected in interstitial tissue but not in seminiferous tubule in sperm. In the case of ovary, adenovirus signal were
localized to the stromal tissue, but no follicular signals were observed. Together, these data provide strong evidence
that the risk of the inadvertent germ-line transmission of vector sequences following intraperitoneal or direct injection into genito-urinary system of adenovirus is extremely low.
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KEYWORD
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adenoviral vector, germ-line transmission, reproductive toxicity
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