Establishment of a new method using pluripotent stem cells and RNA interference and examination of the Htt gene by the method
| Project/Area Number |
25670428
|
|---|
| Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | National Center of Neurology and Psychiatry |
|---|
Principal Investigator |
Hohjoh Hirohiko 国立研究開発法人国立精神・神経医療研究センター, 神経研究所神経薬理研究部, 室長 (60238722)
|
|---|
| Project Period (FY) |
2013-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
|
|---|
| Keywords | 神経変性疾患 / ハンチントン病 / ハンチンチン遺伝子 / RNAi / shRNA / AAV / ES細胞 / Htt / アデノ随伴ウイルス / 多能性幹細胞 / iPS細胞 |
|---|
| Outline of Final Research Achievements |
The role and function of huntingtin (Htt) in cells has been poorly understood. In this study we attempted to obtain novel findings to lead to the elucidation of the Htt functions by a new approach using pluripotent stem cells and a RNA interference (RNAi) technique. Optimal small interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) against Htt have been successfully designed and shRNA-expression adeno-associated viruses (AAVs) have been constructed. Transmission of the constructed shRNA-expression AAV to mouse ES cells for suppressing the endogenous Htt genes was carried out, but resulted in a failure with a pretty low efficiency of AAV infection. A conventional method with synthetic siRNAs and a transfection reagent was also performed; however, the results could not indicate any marked suppression of the target Htt. Accordingly, the research project was unexpectedly difficult; but, it might be achieved if a recent genome-editing technique such as a CRISPR/Cas9 system were used.
|
Report
(4 results)
Research Products
(29 results)
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Ubiquitin C-terminal hydrolase L1 (UCH-L1) act as a novel potentiator of cyclin-dependent kinases to enhance cell proliferation, independent of its hydrolase activity2013
Author(s)
Kabuta, T., Mitsui, T., Takahashi, M., Fujiwara, Y., Kabuta, C., Konya, C., Tsuchiya, Y., Hatanaka, Y., Uchida, K., Hohjoh, H., Wada, K
-
Journal Title
J. Biol. Chem
Volume: 288
Issue: 18
Pages: 12615-12626
DOI
Related Report
Peer Reviewed
-
[Journal Article] Identification of a novel bone morphogenetic protein (BMP)-inducible transcript, BMP-inducible transcript-1, by utilizing the conserved BMP-responsive elements in the Id genes.2013
Author(s)
Shin M, Ohte S, Fukuda T, Sasanuma H, Yoneyama K, Kokabu S, Miyamoto A. Tsukamoto S, Hohjoh H, Jimi E, Katagiri T.
-
Journal Title
J Bone Miner Metab.
Volume: 31
Issue: 1
Pages: 34-43
DOI
NAID
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
