Multimerized self-assembled caged<i>two-in-one</i>siRNA nanoparticles for photomodulation of RNAi-induced gene silencing

Chen, Changmai; Jing, Nannan; Wang, Zhongyu; Chen, Wei; Tang, Xinjing

doi:10.1039/d0sc03562a

Cited by 7 publications

(6 citation statements)

References 42 publications

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“…However, leakage effects of target gene silencing were observed within 48 hours with an increase in cholesterol‐modified caged siRNA concentrations (Figure 2C). Recently, cholesterol‐modified multimerized caged siRNAs have been further designed to photomodulate siRNA gene silencing activity (Figure 2B) [29] . Cholesterol‐modified RNAs were crosslinked with photolabile linkers and then self‐assembled into caged nanoparticles by pairing the bases of two complementary RNA sequences, which greatly inhibited their siRNA activity and enhanced their siRNA stability.…”

Section: Guest‐modified Caged Sirnasmentioning

confidence: 99%

“…Recently, cholesterol-modified multimerized caged siRNAs have been further designed to photomodulate siRNA gene silencing activity (Figure 2B). [29] Cholesterol-modified RNAs were crosslinked with photolabile linkers and then self-assembled into caged nanoparticles by pairing the bases of two complementary RNA sequences, which greatly inhibited their siRNA activity and enhanced their siRNA stability. A two-in-one caged multichol-siGFP/siEg5 could be developed, which could be used to simultaneously photoregulate the RNAi-induced gene silencing of GFP and Eg5 in HepG2 cells upon light irradiation.…”

Section: Cholesterol-modified Caged Sirnasmentioning

confidence: 99%

“…The concentration of the native siGFP (AG/SG, PC) is 5 nM. The image was partially adapted from reference[15] and[29].…”

mentioning

confidence: 99%

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Photoregulation of Gene Expression with Ligand‐Modified Caged siRNAs through Host/Guest Interaction

et al. 2021

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Small interfering RNA (siRNA) can effectively silence target genes through Argonate 2 (Ago2)‐induced RNA interference (RNAi). It is very important to control siRNA activity in both spatial and temporal modes. Among different masking strategies, photocaging can be used to regulate gene expression through light irradiation with spatiotemporal and dose‐dependent resolution. Many different caging strategies and caging groups have been reported for light‐activated siRNA gene silencing. Herein, we describe a novel caging strategy that increases the blocking effect of RISC complex formation/process through host/guest (including ligand/receptor) interactions, thereby enhancing the inhibition of caged siRNA activity until light activation. This strategy can be used as a general approach to design caged siRNAs for the photomodulation of gene silencing of exogenous and endogenous genes.

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Section: Guest‐modified Caged Sirnasmentioning

confidence: 99%

Section: Cholesterol-modified Caged Sirnasmentioning

confidence: 99%

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Photoregulation of Gene Expression with Ligand‐Modified Caged siRNAs through Host/Guest Interaction

et al. 2021

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“…Multimerized self‐assembled caged siRNA nanoparticles were resistant to serum nucleases and RNase A even without cationic condensing reagents. The caged Multi‐Chol‐siGFP/siEg5 nanoparticles targeting both GFP and Eg5 genes were successfully applied to simultaneously photo‐control both GFP and Eg5 gene expression in HepG2 cell as well as GFP gene expression in living mice [26] …”

Section: Photoregulation Of Caged Sirna Functionsmentioning

confidence: 99%

“…The caged Multi-Chol-siGFP/siEg5 nanoparticles targeting both GFP and Eg5 genes were successfully applied to simultaneously photo-control both GFP and Eg5 gene expression in HepG2 cell as well as GFP gene expression in living mice. [26] Near-infrared light with minimal phototoxicity is relatively safe and has the strong tissue penetration than that of UV and visible light. Zhang et al has reported NIR-to-UV upconversion nanoparticles (UCNP) to control the photoactivation and release of DMNPE-caged plasmid DNA (pEGFP) or caged GFP siRNA for photomodulating GFP gene expression in both solution, B16-F0 cells, and in deep tissues.…”

Section: Caged Sirna Nanoparticlesmentioning

confidence: 99%

Photomodulation of Caged RNA Oligonucleotide Functions in Living Systems

et al. 2020

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Using exogenous optical triggers to continuously achieve the precise conditional control of gene expression regulation and dynamic biological processes is one of the central themes of photochemical biology of nucleic acids. Light, a quick and noninvasive stimulus, is a crucial trigger for "off-on" photoswitching of the functions of caged molecules, including peptides and proteins, as well as oligonucleotides. In this Minireview, we mainly focus on photochemical strategies based on caged RNA oligonucleotides for optochemical control of biological functions, including caged siRNA, caged miRNA, and caged guide RNA for CRISPR/Cas9. Light-activated RNA oligonucleotide strategies will exhibit promising applications for exploring the spatiotemporal regulation of specific gene functions and the design of stimuli-sensitive oligonucleotide prodrugs.

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

Chen,

Yu,

et al. 2024

Advanced Science

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Multidrug resistance (MDR) is a major obstacle limiting the effectiveness of chemotherapy against cancer. The combination strategy of chemotherapeutic agents and siRNA targeting drug efflux has emerged as an effective cancer treatment to overcome MDR. Herein, stimuli‐responsive programmable tetrahedral DNA‐RNA nanocages (TDRN) have been rationally designed and developed for dynamic co‐delivery of the chemotherapeutic drug doxorubicin and P‐glycoprotein (P‐gp) siRNA. Specifically, the sense and antisense strand sequences of the P‐gp siRNA, which are programmable bricks with terminal disulfide bond conjugation, are precisely embedded in one edge of the DNA tetrahedron. TDRN provides a stimuli‐responsive release element for dynamic control of functional cargo P‐gp siRNA that is significantly more stable than the “tail‐like” TDN nanostructures. The stable and highly rigid 3D nanostructure of the siRNA‐organized TDRN nanocages demonstrated a notable improvement in the stability of RNase A and mouse serum, as well as long‐term storage stability for up to 4 weeks, as evidenced by this study. These biocompatible and multifunctional TDRN nanocarriers with gold nanocluster‐assisted delivery (TDRN@Dox@AuNCp) are successfully used to achieve synergistic RNAi/Chemo‐therapy in vitro and in vivo. This programmable TDRN drug delivery system, which integrates RNAi therapy and chemotherapy, offers a promising approach for treating multidrug‐resistant tumors.

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Multimerized self-assembled cagedtwo-in-onesiRNA nanoparticles for photomodulation of RNAi-induced gene silencing

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...

Cited by 7 publications

References 42 publications

Photoregulation of Gene Expression with Ligand‐Modified Caged siRNAs through Host/Guest Interaction

Photoregulation of Gene Expression with Ligand‐Modified Caged siRNAs through Host/Guest Interaction

Photomodulation of Caged RNA Oligonucleotide Functions in Living Systems

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

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