Photoinduced RNA interference using DMNPE-caged 2′-deoxy-2′-fluoro substituted nucleic acids in vitro and in vivo

Blidner, Richard A.; Svoboda, Kurt R.; Hammer, Robert P.; Monroe, W. Todd

doi:10.1039/b801532e

Cited by 72 publications

(77 citation statements)

References 49 publications

(88 reference statements)

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“…In fact, uncaging of DMNPEcaged siRNA in solution had demonstrated an efficiency that was comparable to those activated by conventional direct UV light (23,24). Nonetheless, a direct comparison on factors, such as specific dose, duration of irradiation, and percentage restoration of activity between the samples photoactivated using direct UV light and that using NIR light, cannot be made here because the intensity of upconverted UV is comparatively much lower than that from direct UV irradiation, mainly attributed to the significantly low quantum yield of the upconversion process (0.005-0.3%) (31).…”

Section: Discussionmentioning

confidence: 97%

“…Fluorescence emission spectra of UCNs, NIR-to-VIS, NaYF 4 ∶Yb 20%, Er 2% (F); NIRto-NIR, NaYF 4 ∶Yb 0.2%, Tm 0.02% (G); and NIR-to-UV, NaYF 4 ∶Yb 25%, Tm 0.3% UCNs (H), under excitation by an NIR laser at 980 nm, and Inset shows the total fluorescence of NIR-to-UV UCNs in a cuvette, excited by a 980 nm NIR laser. trophotometry (23). In Fig.…”

Section: Resultsmentioning

confidence: 99%

“…1H, and the Inset shows the UCNs were used to prove that caged siRNAs and caged plasmid DNA can be uncaged and activated using NIR-to-UV upconverted light. Various strategies have been undertaken for caging nucleic acids with light-sensitive compounds (22) and caging with 4,5-dimethoxy-2-nitroacetophenone (DMNPE) was found to be effective in caging plasmid DNA and siRNA (7,23). The probable site of attachment of DMNPE to the phosphate backbone of DNA was proposed by Haselton and coworkers (24) Detailed schematic on caging of these nucleic acids with the chemical DMNPE and their uncaging with upconverted UV light emitted from the UCNs is as illustrated in Fig.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Remote activation of biomolecules in deep tissues using near-infrared-to-UV upconversion nanotransducers

Jayakumar

Idris

Zhang

2012

Proc. Natl. Acad. Sci. U.S.A.

344

255

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Controlled activation or release of biomolecules is very crucial in various biological applications. Controlling the activity of biomolecules have been attempted by various means and controlling the activity by light has gained popularity in the past decade. The major hurdle in this process is that photoactivable compounds mostly respond to UV radiation and not to visible or near-infrared (NIR) light. The use of UV irradiation is limited by its toxicity and very low tissue penetration power. In this study, we report the exploitation of the potential of NIR-to-UV upconversion nanoparticles (UCNs), which act as nanotransducers to absorb NIR light having high tissue penetration power and negligible phototoxicity and emit UV light locally, for photoactivation of caged compounds and, in particular, used for photo-controlled gene expression. Both activation and knockdown of GFP was performed in both solution and cells, and patterned activation of GFP was achieved successfully by using upconverted UV light produced by NIR-to-UV UCNs. In-depth photoactivation through tissue phantoms and in vivo activation of caged nucleic acids were also accomplished. The success of this methodology has defined a unique level in the field of photo-controlled activation and delivery of molecules.

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Section: Discussionmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Remote activation of biomolecules in deep tissues using near-infrared-to-UV upconversion nanotransducers

Jayakumar

Idris

Zhang

2012

Proc. Natl. Acad. Sci. U.S.A.

344

255

View full text Add to dashboard Cite

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“…This technique takes advantage of the endogenous RNA interference pathway and, using siRNA or dsRNA modified with photolabile groups, allows RNA interference to be controlled with light. Subsequently, others have also attempted to bring RNA interference under the control of light using a variety of approaches (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Enhanced Light-Activated RNA Interference Using Phosphorothioate-Based dsRNA Precursors of siRNA

Kala

Friedman

2011

Pharm Res

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“…A significant drawback of the method is the instability of the phosphotriester products, leading to RNA fragmentation. [16] The method has not been demonstrated to block hybridization or folding, possibly due to the low numbers of modifications that can be appended.Two chemical blocking strategies for RNA and DNA have been previously reported. [17] In this methods, one or several guanine bases are caged with a trichloroethyl (TCE) [17a] or 4-nitrobenzyl (NB) [17b] groups and incorporated into a nucleic acid strand during solid-phase synthesis.…”

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confidence: 99%

RNA Cloaking by Reversible Acylation

2018

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We describe a selective and mild chemical approach to controlling RNA hybridization, folding, and enzyme interactions. Reaction of RNAs in aqueous buffer with an azide-substituted acylating agent (100-200 mM) yields several 2′-OH acylations per RNA strand in as little as 10 min. This poly-acylated ("cloaked") RNA is strongly blocked from hybridization with complementary nucleic acids, from cleavage by RNA-processing enzymes, and from folding into active aptamer structures. Importantly, treatment with a water-soluble phosphine triggers a Staudinger reduction of the azide groups, resulting in spontaneous loss of acyl groups ("uncloaking"). This fully restores RNA folding and biochemical activity. Graphical abstractChemical switch for RNA: We describe simple selective chemical approach for control of RNA function. Polyacylation of 2′-OH groups with a nicotinyl-imidazole reagent (cloaking) switches off structure and biomolecular recognition. RNA is switched on again (uncloaking) by Staudinger reductions that remove the acyl groups. Keywordscloaking; RNA; caging; acylation; Staudinger The great complexity of RNA biology presents challenges to chemical and biological analysis. Beyond the better-studied messenger RNAs, the largest fraction of cellular RNA consists of noncoding species, including not only transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), but also a growing range of other long and short noncoding species, [1] including small nuclear RNAs (snRNA), [2] microRNAs (miRNA), [3] small nucleolar RNAs Correspondence to: Eric T. Kool. Supporting information for this article is given via a link at the end of the document. HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript (snoRNA), [4] circular RNAs (circRNA), [5] and tRNA fragments (tRF). [6] The biological functions of a major fraction of these species remain to be characterized, and their interactions with other RNAs, proteins, and small molecules remain elusive. Recent advancements in RNA sequencing [7] and in structure mapping [8] have been important in characterizing RNAs, but the field will benefit greatly from new methods as well. For example, studies of interactions and changes that occur with RNA in time and space could benefit from methods to control structure and interactions in a chemically selective way. Moreover, the rapid rise in use of RNA as a diagnostic biomarker might also benefit from methods of controlling its properties in vitro.RNA function can be studied with methods that temporarily suspend its activity. For example, light-based blocking (photocaging) strategies have been used recently in temporal control of RNA activity. [9] In this approach, a photolabile caging group is added onto one or multiple RNA bases, [10] phosphate groups [11] or 2′-OH groups of synthetic oligoribonucleotides. [12] Upon photoirradiation, the cage is released, restoring RNA function. Such photocaging strategies have been used to control and study gene expression [10,11b,13] and ribozyme function. [12b,14] While...

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Photoinduced RNA interference using DMNPE-caged 2′-deoxy-2′-fluoro substituted nucleic acids in vitro and in vivo

Cited by 72 publications

References 49 publications

Remote activation of biomolecules in deep tissues using near-infrared-to-UV upconversion nanotransducers

Remote activation of biomolecules in deep tissues using near-infrared-to-UV upconversion nanotransducers

Enhanced Light-Activated RNA Interference Using Phosphorothioate-Based dsRNA Precursors of siRNA

RNA Cloaking by Reversible Acylation

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