Development of cell replacement therapy for hemophilia using a novel artificial chromosome vector

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K09828
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Tottori University
• Principal Investigator: KUROSAKI Hajime 鳥取大学, 医学(系)研究科(研究院), 助教 (70464295)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 血友病 / 第8因子 / 血栓・止血

Outline of Final Research Achievements

Human and mouse artificial chromosome (HAC and MAC, respectively) vectors have some unique characteristics compared with conventional gene therapy vectors, carrying large transgenes without a size limitation, existing independently from the host genome in cells, which avoids insertional mutagenesis, and showing persistent expression of transgenes. Induced pluripotent stem (iPS) cells have a great potential for gene therapy because they can be derived from an individual’s own tissues. Upon reintroduction, they contribute to the specialized functions of various tissues. Based on these features, we transferred a stable factor VIII expression cassette using a MAC to iPS cells derived from hemophilia A model. These iPS cells gave rise to the three germ layers in teratomas. Moreover, we successfully restored hemostasis in hemophilia model chimeric mice and detected an FVIII antigen in the plasma of these mice. This study has demonstrated a therapeutic effect in this mouse model.

Free Research Field

再生医学

Academic Significance and Societal Importance of the Research Achievements

血友病は単一の遺伝子異常による遺伝性疾患であり、製剤として第8因子を補充する対処療法しかない。遺伝子・細胞補充治療法は、血友病だけでなく筋ジストロフィーのような治療法確立を急務とする疾患にも応用されることが期待されている。また本研究から得られた細胞については第8因子を製剤化する、物質生産のホストとして高いポテンシャルを秘めており、同じく酵素補充療法をターゲットとするような遺伝性疾患にも大きく貢献できる。