Improvement of mouse beta-thalassemia by electrotransfer of erythropoietin cDNA.
Exp Hematol
; 29(3): 295-300, 2001 Mar.
Article
em En
| MEDLINE
| ID: mdl-11274756
ABSTRACT
OBJECTIVE:
A new intramuscular DNA electrotransfer method for erythropoietin (EPO) expression was evaluated in the natural mouse model of human beta-thalassemia (Hbb-thal1) in terms of its ability to reverse the anemia and improve the thalassemic features of erythrocytes. MATERIALS ANDMETHODS:
Intramuscular injection of small amounts of a plasmid encoding mouse EPO, immediately followed by controlled electric pulses, was used.RESULTS:
This procedure induced very high hematocrit levels in beta-thalassemic mice compared to nonelectrotransferred mice. The hematocrit increase was dose dependent, still increased 4 months after injection of plasmid DNA, and associated with a high transgenic EPO blood level in all mice (up to 2500 mU/mL of plasma). EPO gene electrotransfer not only led to a long-lasting and dose-dependent increase in the hematocrit but also to a 100% increase in the lifespan of erythrocytes of thalassemic mice. This was related to a nearly complete reestablishment of alpha/beta globin chain balance, as demonstrated by a marked decrease in unpaired alpha globin chain. Eight months after the first electrotransfer of pCMV-mEPO plasmid, reinjection of the same construct raised the hematocrit to a level close to that observed following the first electrotransfer.CONCLUSION:
This is the first description of the use of plasmid DNA to achieve long-term improvement in a mouse model of a human genetic disorder.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA Recombinante
/
Terapia Genética
/
Eritropoetina
/
Talassemia beta
/
Eletroporação
Limite:
Animals
Idioma:
En
Revista:
Exp Hematol
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
França