2021 Fiscal Year Annual Research Report
Development of nanovesicles with antisense oligonucleotides-embedded membrane and encapsulated RNase H in the cavity for cooperative gene knockdown
| Project/Area Number |
20K22495
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
キム ボブス 東京大学, 大学院工学系研究科(工学部), 特任研究員 (10876460)
|
|---|
| Project Period (FY) |
2020-09-11 – 2022-03-31
|
| Keywords | ASO / vesicle / nanoparticle / RNase H / gene knockdown / gene silencing / co-delivery |
|---|
| Outline of Annual Research Achievements |
A nano-sized vesicular assembly of antisense oligonucleotides (ASOs) is created through the polyion complex formation with poly(ethylene glycol) (PEG)-b-polycations for codelivery of ASOs with their effector enzyme, ribonuclease H. The stability of ASO assemblies is highly affected by the chemical structures of both ASOs and PEG-b-polycations, and a 100 nm-sized, stable ASO-assembled vesicle (ASOsome) is successfully fabricated between the phosphorothioate and locked nucleic acid-installed ASOs and the block catiomers bearing a high degree of guanidino groups. The vesicular assembly of ASO with the enzyme (AWEsome) efficiently introduces ASO together with RNase H into cultured cancer cells and elicits the significantly enhanced gene knockdown efficiency, compared with the ASOsome without RNase H or their simple mixture without encapsulation of RNase H.
|
