Multimerized Self-assembled Caged SiRNA Nanoparticles for Photomodulation of RNAi-induced Gene Silencing

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2021 Jun 7

PMID 34094437

Citations 3

Authors

Changmai Chen

Nannan Jing

Zhongyu Wang

Yu Zhang

Wei Chen

Xinjing Tang

Affiliations

Soon will be listed here.

Abstract

We rationally designed and developed caged siRNA nanoparticles (Multi-Chol-siRNA) self-assembled with cholesterol-modified multimerized caged siRNAs for photomodulation of siRNA gene silencing activity. Strong resistance to serum nuclease and RNase A was observed for these cholesterol-modified caged siRNA nanoparticles due to the formation of nanostructures with high intensity of siRNA. These caged Multi-Chol-siRNA self-assembled nanoparticles were successfully used to achieve photochemical regulation of both exogenous GFP and endogenous Eg5 gene expressions with a GFP/RFP transient transfection system and Eg5-associated assays, respectively. Further, caged Multi-Chol-siGFP/siEg5 self-assembled nanoparticles simultaneously targeting GFP and Eg5 genes were also developed. The caged Multi-Chol-siRNA self-assembled nanoparticles have demonstrated the effectiveness of enhancing photomodulation of multiple RNAi-induced gene silencing activities in cells.

Citing Articles

Programmable Tetrahedral DNA-RNA Nanocages Woven with Stimuli-Responsive siRNA for Enhancing Therapeutic Efficacy of Multidrug-Resistant Tumors.

Chen C, Yu M, Li Q, Zhou Y, Zhang M, Cai S Adv Sci (Weinh). 2024; 11(32):e2404112.

PMID: 38923806 PMC: 11348235. DOI: 10.1002/advs.202404112.

Recent Advancements of Aptamers in Cancer Therapy.

Venkatesan S, Chanda K, Balamurali M ACS Omega. 2023; 8(36):32231-32243.

PMID: 37720779 PMC: 10500573. DOI: 10.1021/acsomega.3c04345.

Translational control of gene function through optically regulated nucleic acids.

Darrah K, Deiters A Chem Soc Rev. 2021; 50(23):13253-13267.

PMID: 34739027 PMC: 8900068. DOI: 10.1039/d1cs00257k.

References

Govan J, Young D, Lusic H, Liu Q, Lively M, Deiters A . Optochemical control of RNA interference in mammalian cells. Nucleic Acids Res. 2013; 41(22):10518-28. PMC: 3905849. DOI: 10.1093/nar/gkt806. View

Janas M, Schlegel M, Harbison C, Yilmaz V, Jiang Y, Parmar R . Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity. Nat Commun. 2018; 9(1):723. PMC: 5818625. DOI: 10.1038/s41467-018-02989-4. View

Zhang Y, Ling X, Su X, Zhang S, Wang J, Zhang P . Optical Control of a CRISPR/Cas9 System for Gene Editing by Using Photolabile crRNA. Angew Chem Int Ed Engl. 2021; 59(47):20895-20899. DOI: 10.1002/anie.202009890. View

Mikat V, Heckel A . Light-dependent RNA interference with nucleobase-caged siRNAs. RNA. 2007; 13(12):2341-7. PMC: 2080613. DOI: 10.1261/rna.753407. View

Hu B, Weng Y, Xia X, Liang X, Huang Y . Clinical advances of siRNA therapeutics. J Gene Med. 2019; 21(7):e3097. DOI: 10.1002/jgm.3097. View

Lee H, Lytton-Jean A, Chen Y, Love K, Park A, Karagiannis E . Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery. Nat Nanotechnol. 2012; 7(6):389-93. PMC: 3898745. DOI: 10.1038/nnano.2012.73. View

Setten R, Rossi J, Han S . The current state and future directions of RNAi-based therapeutics. Nat Rev Drug Discov. 2019; 18(6):421-446. DOI: 10.1038/s41573-019-0017-4. View

Bruck J, Pascolo S, Fuchs K, Kellerer C, Glocova I, Geisel J . Cholesterol Modification of p40-Specific Small Interfering RNA Enables Therapeutic Targeting of Dendritic Cells. J Immunol. 2015; 195(5):2216-23. DOI: 10.4049/jimmunol.1402989. View

Zhao J, Chu H, Zhao Y, Lu Y, Li L . A NIR Light Gated DNA Nanodevice for Spatiotemporally Controlled Imaging of MicroRNA in Cells and Animals. J Am Chem Soc. 2019; 141(17):7056-7062. DOI: 10.1021/jacs.9b01931. View

10.

Schluep T, Lickliter J, Hamilton J, Lewis D, Lai C, Lau J . Safety, Tolerability, and Pharmacokinetics of ARC-520 Injection, an RNA Interference-Based Therapeutic for the Treatment of Chronic Hepatitis B Virus Infection, in Healthy Volunteers. Clin Pharmacol Drug Dev. 2016; 6(4):350-362. PMC: 5516171. DOI: 10.1002/cpdd.318. View

11.

Wu S, Lopez-Berestein G, Calin G, Sood A . RNAi therapies: drugging the undruggable. Sci Transl Med. 2014; 6(240):240ps7. PMC: 4154139. DOI: 10.1126/scitranslmed.3008362. View

12.

Shah S, Rangarajan S, Friedman S . Light-activated RNA interference. Angew Chem Int Ed Engl. 2005; 44(9):1328-32. DOI: 10.1002/anie.200461458. View

13.

Zhang Y, Peng R, Xu F, Ke Y . Hierarchical Self-Assembly of Cholesterol-DNA Nanorods. Bioconjug Chem. 2019; 30(7):1845-1849. PMC: 7254875. DOI: 10.1021/acs.bioconjchem.9b00322. View

14.

Yoo H, Jung H, Kim S, Mok H . Multivalent comb-type aptamer-siRNA conjugates for efficient and selective intracellular delivery. Chem Commun (Camb). 2014; 50(51):6765-7. DOI: 10.1039/c4cc01620c. View

15.

Chen C, Yang Z, Tang X . Chemical modifications of nucleic acid drugs and their delivery systems for gene-based therapy. Med Res Rev. 2018; 38(3):829-869. DOI: 10.1002/med.21479. View

16.

Zhang L, Chen C, Fan X, Tang X . Photomodulating Gene Expression by Using Caged siRNAs with Single-Aptamer Modification. Chembiochem. 2018; 19(12):1259-1263. DOI: 10.1002/cbic.201700623. View

17.

Jain P, Shah S, Friedman S . Patterning of gene expression using new photolabile groups applied to light activated RNAi. J Am Chem Soc. 2010; 133(3):440-6. DOI: 10.1021/ja107226e. View

18.

Lee S, Mok H, Jo S, Hong C, Park T . Dual gene targeted multimeric siRNA for combinatorial gene silencing. Biomaterials. 2010; 32(9):2359-68. DOI: 10.1016/j.biomaterials.2010.11.062. View

19.

Ji Y, Yang J, Wu L, Yu L, Tang X . Photochemical Regulation of Gene Expression Using Caged siRNAs with Single Terminal Vitamin E Modification. Angew Chem Int Ed Engl. 2015; 55(6):2152-6. DOI: 10.1002/anie.201510921. View

20.

Zhang L, Liang D, Wang Y, Li D, Zhang J, Wu L . Caged circular siRNAs for photomodulation of gene expression in cells and mice. Chem Sci. 2018; 9(1):44-51. PMC: 5869302. DOI: 10.1039/c7sc03842a. View