Gene thenapy for renal anemia in mice with polycystic kidney using an adeuovirs vector encoding the human erythropoietin gene

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 07671261
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Juntendo University
• Principal Investigator: SUZUKI Sigenobu JUNTENDO UNIV,ASSISTANT PROFESSOR, 医学部, 講師 (20271281)
• Co-Investigator(Kenkyū-buntansha): OSADA Siori JUNTENDO UNIV,RESEARCH ASSOCIATE, 医学部, 助手 (50296860) ; SETOGUTHI Yasuhiro JUNTENDO UNIV,RESEARCH ASSOCIATE, 医学部, 助手 (90206649)
• Project Period (FY): 1995 – 1997
• Keywords: erythropoietin / renal anemia / mesothelial all / polycystic lindney / gene thrapy / adens virus retor

Research Abstract

Human erythropoietin (HuEPO) gene transfer to mesothelial cells was performed in vitro and in vivo. Recombinant replication-deficient adenoviruss containing HuEPO cDNA (ASCMVEPO), E.coli lacZ gene (AdCMVlacZ), or an endogenous gene driven by the cytomegalovirus promotor/enhancer were constructed. In vitro studies demonstrated that mesothelial cells secreted HuEPO synthesized by the innoculation of AdCMVEPO in a polarized fashion. The sialylated oligosaccharides associated with the HuEPO from AdCMVEPO-treated mesothelial cells occupied 78 +/- 0.7% of the total oligosaccharide pool. For in vivo study, the DBA/2FG-pcy mouse, a model for human autosomal recessive polycystic kindney disease with progressive anemia, was used. A single intraperioneal administration of AdCMVEPO induced HuEPO synthesis in the peritoneum and a marked increase in erythrocyte production. The maximal increase (18 +/- 2%) in hematocrit was observed on day 28, and it remained elevated for 40 days. These results show that intraperitoneal administration of AdCMVEPO improves renal anemia appropriately in DBA/2FG-pcy mice.