Morel Gustavo R, Reggiani Paula C, Console Gloria M, Rimoldi Omar J, Vesenbeckh Silvan M, Garcia-Bravo Margarita M, Rodriguez Silvia S, Brown Oscar A, Goya Rodolfo G
Institute for Biochemical Research-Histology B, Faculty of Medicine, National University of La Plata, Argentina.
Curr Gene Ther. 2008 Feb;8(1):49-53. doi: 10.2174/156652308783688518.
The aim of the present article is to discuss the potential of gene therapy for thymic hormones as a novel therapeutic strategy to treat dyshomeostatic conditions associated with congenital athymia or hypofunction of the endocrine thymus. Recent studies using an adenoviral vector harboring a synthetic gene for the thymic peptide thymulin are reviewed. This adenoviral vector was injected intramuscularly in thymectomized and nude mice as well as in thymectomized rats. Transduced myocytes acted as an ectopic source of thymulin thus restoring circulating thymulin levels to normal values. This restorative effect was long lasting (several months) even though an adenoviral vector was used. In the rat brain, adenovirally-mediated delivery of the synthetic gene for thymulin achieved longer expression than in the case of adenovirally-delivered reporter genes, which is consistent with the reported antiinflammatory activity of thymulin in the brain. Furthermore, neonatal thymulin gene therapy in nude female mice was able to prevent the pituitary and ovarian alterations that typically occur in this mutant after puberty. Neonatal thymulin gene therapy in nude mice was able to prevent some of the alterations in lipid metabolism that develop during adult life in congenitally athymic mice. We conclude that the availability of the above biotechnological tools should boost basic studies on the molecular biology of thymulin and should also allow an assessment of the potential of gene therapy to restore circulating thymulin levels in thymodeficient animal models and eventually, in humans.
本文旨在探讨胸腺激素基因治疗作为一种新型治疗策略，用于治疗与先天性无胸腺或内分泌胸腺功能减退相关的内环境稳态失调病症的潜力。综述了近期使用携带胸腺肽胸腺生成素合成基因的腺病毒载体的研究。该腺病毒载体通过肌肉注射到胸腺切除的裸鼠和大鼠以及胸腺切除的小鼠体内。转导的肌细胞作为胸腺生成素的异位来源，从而使循环胸腺生成素水平恢复到正常水平。即使使用了腺病毒载体，这种恢复效果也能持续很长时间（几个月）。在大鼠脑中，腺病毒介导的胸腺生成素合成基因递送比腺病毒递送的报告基因实现了更长时间的表达，这与胸腺生成素在脑中的抗炎活性报道一致。此外，对裸鼠雌性幼崽进行胸腺生成素基因治疗能够预防该突变体在青春期后通常出现的垂体和卵巢改变。对裸鼠进行胸腺生成素基因治疗能够预防先天性无胸腺小鼠成年后出现的一些脂质代谢改变。我们得出结论，上述生物技术工具的可用性应能推动胸腺生成素分子生物学的基础研究，还应能评估基因治疗在胸腺功能缺陷动物模型以及最终在人类中恢复循环胸腺生成素水平的潜力。
