Development of Ischemia-Specific Oligonucleotide Therapeutics System for Acute stroke
Project/Area Number |
26282136
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Biomedical engineering/Biomaterial science and engineering
|
Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
ISHIBASHI SATORU 東京医科歯科大学, 医歯(薬)学総合研究科, 講師 (30533369)
|
Co-Investigator(Kenkyū-buntansha) |
和田 健彦 東北大学, 多元物質科学研究所, 教授 (20220957)
横田 隆徳 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (90231688)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
|
Keywords | 脳卒中 / 核酸医薬 / 神経保護 / マウス / 人工核酸 / 環境応答型核酸 / 水素イオン指数 / 血管新生 / 脳血管障害 / 虚血応答性核酸 / ヘテロ核酸 / 神経科学 / 脳神経疾患 / 刺激応答性核酸 / 脳梗塞 / 動物モデル / pH |
Outline of Final Research Achievements |
Stroke remains a major cause of mortality and long-term disability worldwide. Recent studies elucidated well the complex pathogenesis of acute ischemic stroke such as dynamic alternation of genes and proteins, which could contribute to develop novel therapeutics for acute stroke. We previously developed an heteroduplex oligonucleotide (HDO), which strongly silenced its target gene in many organs, and a peptide ribonucleic acids (PRNA), which regulated genes expression based on intracellular environmental condition (e.g. pH). By means of these two novel technologies, we aimed to create ischemia-specific oligonucleotide therapeutics system for acute stroke. In our studies, we have successfully developed a novel oligonucleotide, which could specifically and strongly inhibit gene expression in brain early in ischemic stroke and can dramatically influence its phenotype.
|
Report
(4 results)
Research Products
(61 results)
-
-
-
-
-
[Journal Article] Progressive Multifocal Leukoencephalopathy with Balanced CD4/CD8 T-Cell Infiltration and Good Response to Mefloquine Treatment2016
Author(s)
Sanjo N, Kina S, Shishido-Hara Y, Nose Y, Ishibashi S, Fukuda T, Maehara K, Eishi Y, Mizusawa H, Yokota T
-
Journal Title
Internal Medicine
Volume: 55
Issue: 12
Pages: 1631-1635
DOI
NAID
ISSN
0918-2918, 1349-7235
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
[Journal Article] Module Strategy for Peptide Ribonucleic Acid (PRNA)-DNA and PRNA-Peptide Nucleic Acid (PNA)-DNA Chimeras: Synthesis and Interaction of Chimeras with DNA and RNA2016
Author(s)
Uematsu, R.; Inagaki, M.; Asai, M.; Sugai, H.; Maeda, Y.; Nagami, A.; Sato, H.; Sakamoto, S.; Araki, Y.; Nishijima, M.; Inoue, Y.; Wada, T
-
Journal Title
Chemistry Letters
Volume: 45
Issue: 3
Pages: 350-352
DOI
NAID
Related Report
Peer Reviewed
-
-
-
-
[Journal Article] Enhanced Phospholipase A2 Group 3 Expression by Oxidative Stress Decreases the Insulin-Degrading Enzyme2015
Author(s)
Yui D, Nishida Y, Nishina T, Mogushi K, Tajiri M, Ishibashi S, Ajioka I, Ishikawa K, Mizusawa H, Murayama S, Yokota T
-
Journal Title
PLoS One.
Volume: 10
Issue: 12
Pages: e0143518-e0143518
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] A Score for Predicting Paroxysmal Atrial Fibrillation in Acute Stroke Patients: iPAB Score2015
Author(s)
Yoshioka K, Watanabe K, Zeniya S, Ito Y, Hizume M, Kanazawa T, Tomita M, Ishibashi S, Miake H, Tanaka H, Yokota T, Mizusawa H
-
Journal Title
J Stroke Cerebrovasc Dis
Volume: 24
Issue: 10
Pages: 2263-9
DOI
Related Report
Peer Reviewed
-
[Journal Article] Chimeric Antisense Oligonucleotide Conjugated to α- Tocopherol2015
Author(s)
Nishina T, Numata J, Nishina K, Yoshida-Tanaka K, Nitta K, Piao W, Iwata R, Ito S, Kuwahara H, Wada T, Mizusawa H, Yokota T
-
Journal Title
Mol Ther Nucleic Acids
Volume: 4
Pages: e220-e220
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
[Journal Article] Intrathecal AAV Serotype 9-mediated Delivery of shRNA Against TRPV1 Attenuates Thermal Hyperalgesia in a Mouse Model of Peripheral Nerve Injury.2014
Author(s)
Hirai T, Enomoto M, Kaburagi H, Sotome S, Yoshida-Tanaka K, Ukegawa M, Kuwahara H, Yamamoto M, Tajiri M, Miyata H, Hirai Y, Tominaga M, Shinomiya K, Mizusawa H, Okawa A, Yokota T
-
Journal Title
Mol Ther
Volume: 22
Issue: 2
Pages: 409-19
DOI
Related Report
Peer Reviewed
-
[Journal Article] Double Helices of a Pyridine-Appended Zinc Chlorophyll Derivative2013
Author(s)
Y. Shinozaki, G. Richards, K. Ogawa, A. Yamano, K. Ohara, K. Yamaguchi, S. Kawano, K. Tanaka, Y. Araki, T. Wada, and J. Otsuki
-
Journal Title
J. Am. Chem. Soc.
Volume: 135
Issue: 14
Pages: 5262-5265
DOI
Related Report
Peer Reviewed
-
[Presentation] SILENCING OF MALAT1 LONG NON-CODING RNA WITH DNA/RNA HETERODUPLEX OLIGONUCLEOTIDES EXACERBATES CEREBRAL ISCHEMIA2017
Author(s)
Ishibashi S, Li L, Iwasawa E, Song J, Ichijo M, Zhang Y, Piao W, Yoshida K, Kuwahara H, Yoshioka K, Nagata T, Yokota T.
Organizer
XXIII World Congress of Neurology
Place of Presentation
KYOTO INTERNATIONAL CONFERENCE CENTER, Kyoto
Year and Date
2017-09-16
Related Report
Int'l Joint Research
-
[Presentation] GENE SILENCING EFFECT OF HETERODUPLEX OLIGONUCLEOTIDE AND ITS BIODISTRIBUTION IN NEURONS AND BRAIN ENDOTHELIAL CELLS AFTER ISCHEMIA2017
Author(s)
Li L, Ishibashi S, Iwasawa E, Song J, Ichijo M, Zhang Y, Piao W, Yoshida K, Kuwahara H, Yoshioka K, Nagata T, Yokota T
Organizer
XXIII World Congress of Neurology
Place of Presentation
KYOTO INTERNATIONAL CONFERENCE CENTER, Kyoto
Year and Date
2017-09-16
Related Report
Int'l Joint Research
-
[Presentation] Heteroduplex oligonucleotide reduced gene expression in focal ischemic brain in mice2017
Author(s)
Li L, Ishibashi S, Iwasawa E, Song J, Ichijo M, Zhang Y, Piao W, Yoshida K, Kuwahara H, Yoshioka K, Nagata T, Yokota T.
Organizer
STROKE2017
Place of Presentation
大阪国際会議場, 大阪
Related Report
-
-
-
[Presentation] Creation of Ischemia-Specifi c Oligonucleotide Therapeutics System with Intracellular Environmental Condition - Responsive Peptide Ribonucleic Acids (PRNAs)2016
Author(s)
Wada T, Uematsu R, Asai M, Inagaki M, Sugai H, Araki Y, Sakamoto S, Ishibashi S, Yokota T, Wada T
Organizer
The 43nd International Symposium on Nucleic Acids Chemistry
Place of Presentation
Kumamoto Univ, Kumamoto
Year and Date
2016-09-27
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
[Presentation] Creation of the hypoxia-specific oligonucleotide therapeutics system with intracellular environment-responsible peptide ribonucleic acids (PRNAs): Synthesis and antisense activities of new type of chimeric PRNA-DNA derivatives containing phosphoramidate linkage in PRNADNA junction2015
Author(s)
M. Inagaki, R. Uematsu, Y. Araki, S. SAKAMOTO, S. Ishibashi, H. Kashida, H. Asanuma, T. Yokota, T. Wada
Organizer
PACIFICHEM 2015
Place of Presentation
Honolulu, Hawaii, USA
Year and Date
2015-12-15
Related Report
Int'l Joint Research
-
-
-
-
[Presentation] 構造制御に基づく高機能核酸医薬用人工核酸の開 発 ― モデュール法によるペプチドリボ核酸(PRNA)の構造・ 機能制御への新戦略2015
Author(s)
和田健彦, 上松亮平, 菅井祥加, 浅井光夫, 稲垣 雅仁, 荒木保幸, 坂本清志, 樫田啓, 浅沼浩之, 石橋哲, 横田隆徳
Organizer
第64回高分子討論会
Place of Presentation
東北大学(宮城県仙台市)
Year and Date
2015-09-15
Related Report
-
-
-
-
-
-
-
-
-
-
-