Development of the parathyroid hormone production controlling method by the RNA interference in consideration of clinical application

• Project/Area Number: 22590916
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Tokai University
• Principal Investigator: TANAKA Reika 東海大学, 医学部, 講師 (10372947)
• Co-Investigator(Kenkyū-buntansha): KANAI Genta 東海大学, 医学部, 助教 (00535221) ; SAWADA Kaichiro 東海大学, 医学部, 講師 (10420952) ; KAKUTA Takatoshi 東海大学, 医学部, 准教授 (50276854)
• Project Period (FY): 2010-10-20 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 副甲状腺機能亢進症 / 二次性副甲状腺機能亢進症 / ＲＮＡ干渉 / RNA干渉 / 副甲状腺ホルモン

Research Abstract

Considering the safety to clinical application of gene therapy for secondary hyperparathyroidism (2HPT), we attempted the establishment of the RNA interference system in order to prevent damaging patient's genomes. Expression of miRNA for human parathyroid hormone (hPTH) was controlled with tetracycline inducible promotor in modified HEK293 cells which express hPTH constitutively. The cells were transplanted into nudemice, and secretion of hPTH into serum was confirmed. As the decrease of hPTH concentration in serum by feeding doxycycline was shown, the validity of this system was checked.
In parallel to this, the survey of new target genes applied to this system found c-myc and p27Kip1, genes related with apoptosis of parathyroid cells.