Thymus and aging: potential of gene therapy for restoration of endocrine thymic function in thymus-deficient animal models.
OBJECTIVE
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 states associated with athymia, as Di George syndrome, or hypothymic conditions like those associated with AIDS, chronic stress or aging. First we review the advantages of the athymic (nude) mouse as an animal model to implement experimental thymic hormone gene therapy strategies to restore endocrine thymic function. The aging rat, known to be markedly hypothymic, is also considered as an alternative model.
The possibility of constructing adenoviral vectors harboring a synthetic gene for the thymic hormone thymulin is discussed. The adenoviral vector so constructed would then be injected intramuscularly in nude mice or senile rats. Transduced myocytes should then begin to act as an ectopic source of thymulin thus restoring circulating thymulin levels to normal youthful levels.


CONCLUSIONS
We conclude that the implementation of thymulin gene therapy should provide novel biotechnological tools that will boost basic studies on the molecular biology of thymulin and would also allow an assessment of the potential of gene therapy to restore circulating thymulin levels in thymodeficient animal models.
Goya
Rodolfo G
RG
Institute for Biochemical Research at La Plata (INIBIOLP), Faculty of Medicine, National University of La Plata, Argentina. Goya@isis.unlp.edu.ar
Cónsole
Gloria  M
G
Hereñú
Claudia  B
C
Brown
Oscar  A
O
Rimoldi
Omar J
OJ
D000256:Adenoviridae / Q000235:genetics; D000375:Aging / Q000502:physiology*; D000818:Animals; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use; D007113:Immunity, Innate / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D051381:Rats; D013935:Thymic Factor, Circulating / Q000235:genetics* / Q000378:metabolism; D013950:Thymus Gland / Q000002:abnormalities* / Q000502:physiology
D013935:Thymic Factor, Circulating