Treatment of renal fibrosis by short miRNA mimic

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16101
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Tokyo Medical University
• Principal Investigator: Saito Suguru 東京医科大学, 医学部, 臨床研究医 (30793385)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 腎線維症 / AAV / micro RNA / miR-29b

Outline of Final Research Achievements

Renal fibrosis is a common feature of CKD, which has no available specific treatment. Previous studies showed that miR-29b inhibits renal fibrosis in mice models. However, an efficient method of kidney-targeted miRNA delivery has yet to be established.
Recombinant adeno-associated virus (rAAV) vectors have great potential for clinical application. The distinct AAV serotypes exhibit different tissue tropisms. For kidney-targeted gene delivery, the most suitable AAV serotype has yet to be established. We found that rAAV6 vector is the most suitable for targeting kidney cells regardless of animal species in vitro and rAAV6 is the most suitable vector for kidney-targeted in vivo gene delivery in mice. Intra-renal pelvic injection of rAAV vectors can transduce genes into kidney TECs. Furthermore, rAAV6-mediated miR-29b delivery attenuated renal fibrosis in UUO model by suppressing Snail1 expression.

Free Research Field

腎臓内科学分野

Academic Significance and Societal Importance of the Research Achievements

腎間質線維化は糖尿病，高血圧など様々な病態が原因とされており，一度起きた線維化は不可逆的である．一般に慢性腎臓病の初期は糸球体病変であり、これに対しては様々な治療法が存在するが，その後進行が進み，間質線維化が病態の中心になると，人工透析導入の大きな原因となっている．そのため腎間質線維化の抑制を治療目標とすることで，将来的に人工透析導入数の減少を目指すことが可能であると考える．
本研究の成果により，腎線維症の治療法としてmiRNA補充療法を実用化するための可能性を見い出せたと考える．またAAVは臨床応用可能なウイルスベクターであり，腎臓への遺伝子治療においても意義ある成果を残せたと考える．