Gene therapy for long-term restoration of circulating thymulin in thymectomized mice and rats

Gene Therapy
Paula C ReggianiR G Goya

Abstract

Thymulin is a thymic peptide possessing hypophysiotropic activity and antiinflammatory effects in the brain. We constructed a synthetic DNA sequence encoding met-FTS, a biologically active analog of thymulin, and subsequently cloned it into different expression vectors. A sequence optimized for expression of met-FTS in rodents, 5'-ATGCAGGCCAAGTCGCAGGGGGGGTCGAACTAGTAG-3', was cloned in the mammalian expression vectors pCDNA3.1(+) and phMGFP (which expresses the Monster Green Fluorescent Protein), thus obtaining pcDNA3.1-metFTS and p-metFTS-hMGFP, which express met-FTS and the fluorescent fusion protein metFTS-hMGFP, respectively. The synthetic sequence was also used to construct the adenoviral vector RAd-metFTS, which expresses met-FTS. Transfection of HEK293 and BHK cells with pcDNA3.1-metFTS (experimental groups) or pcDNA3.1 (control), led to high levels of thymulin bioactivity (>600 versus <0.1 pg/ml in experimental and control supernatants, respectively). Transfection of HEK293 and BHK cells with pmetFTS-hMGFP revealed a cytoplasmic and nuclear distribution of the fluorescent fusion protein. A single intramuscular (i.m.) injection (10(7) plaque forming units (PFU)/mouse or 10(8) PFU/rat) of RAd-metFTS in thymectomized animal...Continue Reading

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Citations

Nov 24, 2006·Lipids·Margarita M García de BravoRodolfo G Goya
Mar 29, 2007·American Journal of Physiology. Endocrinology and Metabolism·Rodolfo G GoyaMireille Dardenne
Sep 29, 2011·Neuroimmunomodulation·Paula C ReggianiRodolfo G Goya
Jan 9, 2010·Expert Opinion on Therapeutic Targets·Mário SantosAdelino Leite-Moreira
Jul 12, 2012·Life Sciences·Paula C ReggianiGloria M Cónsole
Feb 25, 2009·Annals of the New York Academy of Sciences·Paula C ReggianiRodolfo G Goya
May 24, 2006·Brain Research Bulletin·Gustavo R MorelRodolfo G Goya
Feb 22, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Adriana L da SilvaMarcelo M Morales
Feb 27, 2010·Expert Review of Endocrinology & Metabolism·Silvia S RodriguezGloria M Console

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