Long-term expression of the human beta-globin gene after retroviral transfer into pluripotent hematopoietic stem cells of the mouse.
Adv Exp Med Biol
; 271: 135-48, 1989.
Article
em En
| MEDLINE
| ID: mdl-2486280
ABSTRACT
We have studied the regulation of the human beta-globin gene after retroviral transfer into a variety of transformed and normal hematopoietic cells. After transfer into murine erythroleukemia cells (MEL) expression from the human beta-globin gene responds to inducers of erythroid maturation in parallel to the endogenous murine globin genes. After infection of human BFU-E, RNA expression from the virally-transferred beta-globin gene was measured at 2.5%-5% of the endogenous beta-globin level. The most improved globin vectors can transfer the human beta-globin gene into pluripotent hematopoietic stem cells in mouse bone marrow. Mice reconstituted with infected marrow show human beta-globin RNA and protein expression in peripheral blood cells for over 4 months. In these animals, both myeloid and lymphoid cells carry the integrated provirus at a level of about 1 copy per cell. In serial transplantation experiments, bone marrow from these animals is capable of repopulating secondary and tertiary recipient animals which go on to show long-term human beta-globin expression. Retroviral vectors thus provide a practical way to refine models of globin gene regulation through in vivo tests and to evaluate the feasibility of protocols for gene addition therapy.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Globinas
/
Células-Tronco Hematopoéticas
/
Transfecção
/
Regulação da Expressão Gênica
/
Vetores Genéticos
Tipo de estudo:
Guideline
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Adv Exp Med Biol
Ano de publicação:
1989
Tipo de documento:
Article