Gene therapy using non-viral peptide vector in a canine systemic lupus erythematosus model.
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.
Choi
Eun-Wha
EW
Department of Veterinary Clinical Pathology, College of Veterinary Medicine, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Shin
Il-Seob
IS
Youn
Hwa-young
HY
Kim
Dae-Yong
DY
Lee
Hang
H
Chae
Young-Jin
YJ
Lee
Chang-Woo
CW
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D060908:CTLA-4 Antigen; D003404:Creatinine / Q000652:urine; D004283:Dog Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004285:Dogs; D005260:Female; D005455:Fluorescent Antibody Technique; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006651:Histocytochemistry; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011507:Proteinuria / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic
D000974:Antibodies, Antinuclear; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001323:Autoantibodies; D060908:CTLA-4 Antigen; D007127:Immunoglobulin Constant Regions; D003404:Creatinine