Serial bone marrow transplantation reveals in vivo expression of the pCLPG retroviral vector

Autor(es)

Fratini, Paula ^{[1, 2, 3]} ; Strauss, Bryan E. ^{[1, 2, 3]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Programa Interunidades Biotecnol, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Lab Genet Cardiol Mol LIM 13, Setor Vetores Virais, Fac Med, Inst Coracao, BR-05403900 Sao Paulo - Brazil

^[3] Esplanada Minist, Minist Ciencia & Tecnol, Inst Milenio Rede Terapia Gen, BR-70067900 Brasilia, DF - Brazil

• Tipo de documento: Artigo Científico
• Fonte: VIROLOGY JOURNAL; v. 7, JAN 22 2010.
• Citações Web of Science: 0

Resumo

Background: Gene therapy in the hematopoietic system remains promising, though certain aspects of vector design, such as transcriptional control elements, continue to be studied. Our group has developed a retroviral vector where transgene expression is controlled by p53 with the intention of harnessing the dynamic and inducible nature of this tumor suppressor and transcription factor. We present here a test of in vivo expression provided by the p53-responsive vector, pCLPG. For this, we used a model of serial transplantation of transduced bone marrow cells. Results: We observed, by flow cytometry, that the eGFP transgene was expressed at higher levels when the pCLPG vector was used as compared to the parental pCL retrovirus, where expression is directed by the native MoMLV LTR. Expression from the pCLPG vector was longer lasting, but did decay along with each sequential transplant. The detection of eGFP-positive cells containing either vector was successful only in the bone marrow compartment and was not observed in peripheral blood, spleen or thymus. Conclusions: These findings indicate that the p53-responsive pCLPG retrovirus did offer expression in vivo and at a level that surpassed the non-modified, parental pCL vector. Our results indicate that the pCLPG platform may provide some advantages when applied in the hematopoietic system. (AU)

• Processo FAPESP: 07/50210-0 - Combinacoes estrategicas entre os promotores virais e transgenes destinadas a terapia genica do cancer.
• Beneficiário: Bryan Eric Strauss
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 00/12156-5 - Estratégias de regulação transcricional em produção e expressão de retrovírus
• Beneficiário: Bryan Eric Strauss
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 03/08822-8 - Expressão do sistema retroviral pCLpG medido em recipientes de transplante de medula óssea
• Beneficiário: Paula Fratini
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto