Protein Spherical Nucleic Acids for Live-Cell Chemical Analysis

Samanta, Devleena; Ebrahimi, Sasha; Kusmierz, Caroline D.; Cheng, Ho Fung; Mirkin, Chad A.

doi:10.1021/jacs.0c06866

Cited by 67 publications

(84 citation statements)

References 46 publications

(69 reference statements)

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“…While the metallic gold core provides a means of sensing and tracking the intracellular fate of the nanoconstructs ( Mirkin et al, 1996 ; Cutler et al, 2012 ), it has limited therapeutic use. Thus, later generations of SNAs that have been developed contain biocompatible cores such as such proteins ( Brodin et al, 2015 ; Samanta et al, 2020 ) and liposomes ( Banga et al, 2014 ).…”

Section: General Structure Of Nucleic Acid Carriers and Mechanism Of mentioning

confidence: 99%

Viral Mimicry as a Design Template for Nucleic Acid Nanocarriers

et al. 2021

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Therapeutic nucleic acids hold immense potential in combating undruggable, gene-based diseases owing to their high programmability and relative ease of synthesis. While the delivery of this class of therapeutics has successfully entered the clinical setting, extrahepatic targeting, endosomal escape efficiency, and subcellular localization. On the other hand, viruses serve as natural carriers of nucleic acids and have acquired a plethora of structures and mechanisms that confer remarkable transfection efficiency. Thus, understanding the structure and mechanism of viruses can guide the design of synthetic nucleic acid vectors. This review revisits relevant structural and mechanistic features of viruses as design considerations for efficient nucleic acid delivery systems. This article explores how viral ligand display and a metastable structure are central to the molecular mechanisms of attachment, entry, and viral genome release. For comparison, accounted for are details on the design and intracellular fate of existing nucleic acid carriers and nanostructures that share similar and essential features to viruses. The review, thus, highlights unifying themes of viruses and nucleic acid delivery systems such as genome protection, target specificity, and controlled release. Sophisticated viral mechanisms that are yet to be exploited in oligonucleotide delivery are also identified as they could further the development of next-generation nonviral nucleic acid vectors.

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Section: General Structure Of Nucleic Acid Carriers and Mechanism Of mentioning

confidence: 99%

Viral Mimicry as a Design Template for Nucleic Acid Nanocarriers

et al. 2021

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“…Thin layer chromatography (TLC) measurements were carried out using Merck 60 F254silica gel plates (Merck Millipore, MA, USA); compounds were visualized with a standard handheld short-wave UV lamp (254 nm). 1 H NMR spectra were obtained using a 400 MHz Bruker Digital NMR AVANCE NEO 400 system (Bruker Japan, Kanagawa, Japan), and chemical shifts were reported in parts per million (ppm δ) relative to the solvent (DMSO-d6: 2.49 ppm). Dynamic light scattering (DLS) measurements were carried out using a Malvern Zetasizer Nano ZS (Malvern Instruments, Worcestershire, UK).…”

Section: Reagents and Chemicalsmentioning

confidence: 99%

“…The residue was purified by reprecipitation from methanol, filtered, and dried under diminished pressure to give the PC-CI as an yellow powder (18 mg, yield; 30%). 1…”

Section: Synthesis Of Poly(carbamate) Derivatives Possessing a Carbonylimidazole Moiety At The Polymer End (Pc-ci)mentioning

confidence: 99%

“…Spherical nucleic acids (SNAs) consisting of a nanostructure core densely modified with a brush structure of oligomeric nucleic acids (oligoDNAs) have been widely investigated for decades for various bioanalytical applications, such as sensing, 1 imaging, 2,3 and diagnostics. 4,5 Of interest, negatively charged oligoDNAs on these nanostructures lead to an improved colloidal stability of the nanoparticles in physiological solutions, and enhances the resistance to nuclease degradation, as well as enhancing the ability to bind to complementary oligoDNAs.…”

Section: Introductionmentioning

confidence: 99%

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Preparation of Spherical Nucleic Acid Nanoparticles Containing a Self-immolative Poly(carbamate) Core

et al. 2021

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We prepared a novel spherical nucleic acid, containing a core structure of self-immolative poly(carbamate) (PC), with aminobenzyl alcohol as a repeating unit, by conjugating an end-activated PC derivative with an amine-terminated oligoDNA on a solid support for PC-oligoDNA. Dynamic light-scattering measurements revealed a hydrodynamic diameter of 107 nm with a narrow size distribution. A fluorescent monomer with aminobenzyl alcohol is available for PC-oligoDNA synthesis to enhance the fluorescence emission by a domino-like disassembly of PC in response to various external stimuli.

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“…Fluorescence imaging is a powerful, noninvasive imaging modality used in cell biology. 21 − 23 Its high sensitivity and spatial resolution allow for the detection of a variety of biological targets. 24 , 25 Fluorescence resonance energy transfer (FRET) is a distance-dependent dipolar interaction between two fluorophores that can unlock detailed information on the nanometer scale.…”

Section: Introductionmentioning

confidence: 99%

A Coumarin–Porphyrin FRET Break-Apart Probe for Heme Oxygenase-1

et al. 2021

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Heme oxygenase-1 (HO-1) is a vital enzyme in humans that primarily regulates free heme concentrations. The overexpression of HO-1 is commonly associated with cardiovascular and neurodegenerative diseases including atherosclerosis and ischemic stroke. Currently, there are no known chemical probes to detect HO-1 activity, limiting its potential as an early diagnostic/prognostic marker in these serious diseases. Reported here are the design, synthesis, and photophysical and biological characterization of a coumarin–porphyrin FRET break-apart probe to detect HO-1 activity, Fe–L 1 . We designed Fe–L 1 to “break-apart” upon HO-1-catalyzed porphyrin degradation, perturbing the efficient FRET mechanism from a coumarin donor to a porphyrin acceptor fluorophore. Analysis of HO-1 activity using Escherichia coli lysates overexpressing hHO-1 found that a 6-fold increase in emission intensity at 383 nm was observed following incubation with NADPH. The identities of the degradation products following catabolism were confirmed by MALDI-MS and LC–MS, showing that porphyrin catabolism was regioselective at the α-position. Finally, through the analysis of Fe–L 2 , we have shown that close structural analogues of heme are required to maintain HO-1 activity. It is anticipated that this work will act as a foundation to design and develop new probes for HO-1 activity in the future, moving toward applications of live fluorescent imaging.

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Protein Spherical Nucleic Acids for Live-Cell Chemical Analysis

Cited by 67 publications

References 46 publications

Viral Mimicry as a Design Template for Nucleic Acid Nanocarriers

Viral Mimicry as a Design Template for Nucleic Acid Nanocarriers

Preparation of Spherical Nucleic Acid Nanoparticles Containing a Self-immolative Poly(carbamate) Core

A Coumarin–Porphyrin FRET Break-Apart Probe for Heme Oxygenase-1

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