Development of nanovesicles with antisense oligonucleotides-embedded membrane and encapsulated RNase H in the cavity for cooperative gene knockdown
Project/Area Number |
20K22495
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0403:Biomedical engineering and related fields
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Research Institution | The University of Tokyo |
Principal Investigator |
Kim Beob Soo 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
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | polymeric vesicle / oligonucleotide / antisense / polyplex / encapsulation / RNase H / gene knockdown / codelivery / ASO / vesicle / nanoparticle / gene silencing / co-delivery / antisenseoligonucleotide |
Outline of Research at the Start |
Polymeric nanovesicle comprising ASO and RNase H will be prepared with non-covalent stabilization and co-encapsulation technique. This strategy will provide a versatile platform that allows for the enhanced cooperative functions between small nucleic acids and enzymes.
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Outline of Final Research Achievements |
In this study, vesicular PICs were fabricated using a series of chemically modified SSOs or HDO and guanidinylated PEG-b- polypeptides for the stable codelivery of SSO with RNase H into cultured cells. The 100 nm sized vesicular structure was successfully stabilized in physiological milieu by a polyion pair of PS-Gapmer SSO and PEG-P(Asp-AG/G80). Particularly, both single-stranded, PS backbone oligonucleotides and guanidinylated polypeptides are crucial for the stable nano- vesicle formation in the physiological milieu, presumably due to their enhanced noncovalent interactions, including hydro- phobicity and polyion-pairing capacity. The stabilized SSO- embedded nanovesicle (SSOsome) effectively encapsulated RNase H through physical entrapment using simple vortex- mixing. The RNase H-encapsulated SSOsome (H/SSOsome) enabled the efficient codelivery of SSO and RNase H into cultured cancer cells, leading to the significantly enhanced gene knockdown effect with negligible cytotoxicity.
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Academic Significance and Societal Importance of the Research Achievements |
This strategy can provide a versatile platform that allows for enhanced cooperative functions between small nucleic acids and enzymesFurther, and can be expanded for multimodal bioreactors or theragnostic vehicles by additionally encapsulating varying hydrophilic substances into the cavity.
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Report
(3 results)
Research Products
(1 results)