Gene therapy using non-viral peptide vector in a canine systemic lupus erythematosus model |
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Authors: | Choi Eun-Wha Shin Il-Seob Youn Hwa-young Kim Dae-Yong Lee Hang Chae Young-Jin Lee Chang-Woo |
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Affiliation: | Department of Veterinary Clinical Pathology, College of Veterinary Medicine, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul 151-742, South Korea. |
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Abstract: | Although viral vectors are commonly used for therapeutic gene delivery, their applications are limited due to their specific cell membrane receptor-mediated infection and host immune response. In the present study, we constructed a non-viral peptide vector and applied it in the treatment of experimentally induced systemic lupus erythematosus-like disease in dogs. For therapeutic gene construction, the extracellular domain of canine CTLA-4, and the CH2-CH3 domains of canine immunoglobulin alpha constant region were inserted between the cytomegalovirus promoter and poly-adenylation sequence of bovine growth hormone. The constructed therapeutic gene was ligated to the non-viral synthetic peptide vector and was applied to systemic lupus erythematosus-like disease induced dogs. After gene therapy, clinical signs of systemic lupus erythematosus were reduced dramatically: the anti-nuclear antibody titers and urine protein/creatinine ratios were recovered to normal values, and the skin regained its normal histological features. The peptide vector did not show either tissue specific tropism or host induced immune response. |
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