Establishment of the next generation treatment for hemophilia A by autologous cell implantation

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293237
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Nara Medical University
• Principal Investigator: Shima Modori 奈良県立医科大学, 医学部, 教授 (30162663)
• Co-Investigator(Kenkyū-buntansha): MATSUI Hideto 奈良県立医科大学, 医学部, 講師 (00571027) ; HOTTA Akitsu 京都大学, iPS細胞研究所, 特定拠点助教 (50578002)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: hemophilia A / gene therapy / piggyBack / transposon

Outline of Final Research Achievements

In the current gene and cell-based therapy, there are concerns over the safety of the systemic delivery of conventional viral vectors such as adverse immunological reactions or virus-mediated cytotoxicity. We established non-viral hydrodynamic gene delivery (HGD)　using piggyBack transposon vector. We tested the HGD in hemophilia A mouse model with the combination of non-viral piggyBack transposon vectors which can transfer the full-length FVIII transgene. As a result, we confirmed the sustained FVIII expression for over 300 days without any immune responses. Nextly, we focused on an assessment of the safety of liver-target HGD　of the piggyBack transposon vector in dogs. Liver-targeted HGD was performed using piggyBack transposon vector expressing either GFP or FVIII. By histological examination of liver samples, approximately 70-80% of hepatocytes in all 4 lobes were positive with GFP 120 days after HGD.

Free Research Field

小児血液学