| Project/Area Number |
18K19901
|
|---|
| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Medium-sized Section 90:Biomedical engineering and related fields
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
Cabral Horacio 東京大学, 大学院工学系研究科(工学部), 准教授 (10533911)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
内田 智士 東京大学, 大学院工学系研究科(工学部), 特任助教 (20710726)
|
|---|
| Project Period (FY) |
2018-06-29 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
|
|---|
| Keywords | mRNA / aptamer / polymer / theophyline / triggered translation / theophylline / protein translatiokn / hybridization / polymeric nanocarrier / アプタマー / ナノメディシン |
|---|
| Outline of Final Research Achievements |
We developed mRNA-aptamer hybrids by combining mRNAs, and aptamers having a sequence for hybridization with mRNA and a binding site for theophylline. Two aptamers were constructed and their affinity to theophylline was studied by surface plasmon resonance. Then, PEG-theophylline conjugates were prepared by condensation reaction with PEG-NH2. When the polymer was mixed with the mRNA-aptamer hybrids, it coated the mRNA-aptamer hybrids, forming neutral nanoparticles of 50 nm in diameter. Conversely, mRNA-aptamer hybrids were negatively charged, which confirmed PEG coating. The nanoparticles were de-coated by adding free theophylline, which recovered the negative charge of the hybrids. mRNA-aptamers translated proteins in cell free systems, and this translation was inhibited when coated with PEG-theophylline. After adding theophylline, the protein translation was recovered, indicating that mRNA-aptamers-polymer nanoparticles can sense the surroundings.
|
| Academic Significance and Societal Importance of the Research Achievements |
We demonstrated the potential of our approach for developing systems triggering protein translation after sensing specific molecules. Our findings will foster novel mRNA systems triggering protein expression based on pathological signals. Further studies with aptamers for cancer markers are ongoing.
|
