Expression of human factor IX in mice after injection of genetically modified myoblasts.
AUTOR(ES)
Yao, S N
RESUMO
Hemophilia B is an X chromosome-linked recessive bleeding disorder. To develop a somatic gene therapy for this disease, we have examined whether mouse skeletal myoblasts can serve as efficient vehicles for systemic delivery of recombinant factor IX. When mouse myoblasts (C2C12) transduced with a Moloney murine leukemia virus-based vector containing the bacterial beta-galactosidase gene were injected into mouse skeletal muscles, they fused with the existing and regenerating myofibers and continued to express beta-galactosidase. C2C12 myoblasts that were infected with recombinant retroviruses containing a human factor IX cDNA secreted biologically active human factor IX cDNA secreted biologically active human factor IX into the culture medium at a rate of 2.6 micrograms per 10(6) cells per day. Myotubes derived from these cells in culture continued to express human factor IX (0.68 micrograms/day from myotubes derived from 10(6) C2C12 cells). After injection of the transduced C2C12 myoblasts into skeletal muscles of mice, the systemic level of recombinant human factor IX was found to be as high as approximately 1 microgram/ml of serum. These results provide the rationale for using skeletal myoblasts as an efficient gene delivery vehicle in the somatic gene therapy for hemophilia B.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=48866Documentos Relacionados
- Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adeno-associated virus vectors
- Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus
- Successful expression of human factor IX following repeat administration of adenoviral vector in mice.
- Gene therapy via primary myoblasts: long-term expression of factor IX protein following transplantation in vivo.
- Differences among myosins synthesized in non-myogenic cells, presumptive myoblasts, and myoblasts.