Sequence-programmable covalent bonding of designed DNA assemblies

Gerling, Thomas; Kube, Massimo; Kick, Benjamin; Dietz, Hendrik

doi:10.1126/sciadv.aau1157

Cited by 192 publications

(217 citation statements)

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“…[2][3][4][5] In recenty ears, programmable DNA origami nanostructures (DONs) [6][7][8][9][10] have been considered promising candidates for the development of tailored and multifunctional drug-delivery vehicles. [17,[22][23][24][25] Herein, we study DON digestion by endonucleases (DNase I) in dependence of DON superstructure. [15] However,c oncerns have been raised regarding the stabilityo fD ONs and their performance in biological media.…”

mentioning

confidence: 99%

“…[16, 17] Although it has been shown that DONs can survive under low-cation conditions, [18,19] stability studies performedi n serum or cell culture media have yielded somewhat controversial and quite distinct results. The designed DONs are not treated with any stabilitymodulating approaches, [17] such as methylation [29] or crosslinking, [25] and thus, they represent the most commonly used form of DNA origami.O ur results reveal that digestion of these DONs indeed exhibits ad ependence on superstructure. [17,[22][23][24][25] Herein, we study DON digestion by endonucleases (DNase I) in dependence of DON superstructure.…”

mentioning

confidence: 99%

“…DNase Ii sw idely present in serum and varioust issues,w hich makes it one of the most relevantt hreatst ot he stability of DONs in vivo. The designed DONs are not treated with any stabilitymodulating approaches, [17] such as methylation [29] or crosslinking, [25] and thus, they represent the most commonly used form of DNA origami.O ur results reveal that digestion of these DONs indeed exhibits ad ependence on superstructure. [8,16] Therefore, thesea pproaches can only resolve the time points at which the whole or most of the nanostructure has been digested.…”

mentioning

confidence: 99%

“…[8,15,[19][20][21] Therefore, significant efforts have been madei nto coating ands tabilizing DONs under biologically relevant conditions. [17,[22][23][24][25] Herein, we study DON digestion by endonucleases (DNase I) in dependence of DON superstructure. DNase Ii sw idely present in serum and varioust issues,w hich makes it one of the most relevantt hreatst ot he stability of DONs in vivo.…”

mentioning

confidence: 99%

“…Previously,D ON cleavage by endonucleases was studied by employing ratherl ong timescales. The designed DONs are not treated with any stabilitymodulating approaches, [17] such as methylation [29] or crosslinking, [25] and thus, they represent the most commonly used form of DNA origami.O ur results reveal that digestion of these DONs indeed exhibits ad ependence on superstructure. Moreover,t hese experiments could neither reveals patial variations of DNase Is usceptibility within as ingle DON, nor facilitate parallel comparison of different structures under the same conditions.…”

mentioning

confidence: 99%

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Real‐Time Observation of Superstructure‐Dependent DNA Origami Digestion by DNase I Using High‐Speed Atomic Force Microscopy

et al. 2019

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GuidoG rundmeier, [a] AdrianK eller,* [a] andV eikkoL inko* [a, b, c] DNA nanostructures have emerged as intriguing tools for numerous biomedical applications. However, in many of those applicationsa nd most notably in drug delivery,t heir stability and function may be compromised by the biological media. A particularly important issue for medicala pplications is their interaction with proteins such as endonucleases, which may degrade the well-defined nanoscale shapes.H erein, fundamental insights into this interaction are provided by monitoring DNase Id igestion of four structurally distinct DNA origami nanostructures (DONs) in real time and at as ingle-structure level by using high-speed atomic force microscopy.T he effect of the solid-liquidi nterface on DON digestioni sa lso assessed by comparison with experiments in bulk solution. It is shown that DON digestion is strongly dependentoni ts superstructure and flexibility and on the local topology of the individual structure.The rapidly evolvingf ield of DNA nanotechnology enables custom fabrication of various nanoscale shapes with unprecedented addressability; [1] these have found some fascinating implementations in materials science and especiallyi nm any biochemicala nd biophysical systems. [2][3][4][5] In recenty ears, programmable DNA origami nanostructures (DONs) [6][7][8][9][10] have been considered promising candidates for the development of tailored and multifunctional drug-delivery vehicles. [11][12][13][14] For therapeutic in vivo applications, the DON vehicles should preferably be compatible with the immunes ystem, resistant to nucleases, have as ufficiently long circulation half-life, and be able to maintain their shape at the ionic strengths of the biological fluids. [15] However,c oncerns have been raised regarding the stabilityo fD ONs and their performance in biological media. [16, 17] Although it has been shown that DONs can survive under low-cation conditions, [18,19] stability studies performedi n serum or cell culture media have yielded somewhat controversial and quite distinct results. [8,15,[19][20][21] Therefore, significant efforts have been madei nto coating ands tabilizing DONs under biologically relevant conditions. [17,[22][23][24][25] Herein, we study DON digestion by endonucleases (DNase I) in dependence of DON superstructure. DNase Ii sw idely present in serum and varioust issues,w hich makes it one of the most relevantt hreatst ot he stability of DONs in vivo. Previously,D ON cleavage by endonucleases was studied by employing ratherl ong timescales. [8,16] Therefore, thesea pproaches can only resolve the time points at which the whole or most of the nanostructure has been digested. Moreover,t hese experiments could neither reveals patial variations of DNase Is usceptibility within as ingle DON, nor facilitate parallel comparison of different structures under the same conditions. Herein, we thus employ high-speed atomicf orce microscopy (HS-AFM) [26] to study the degradation of four well-established and structurally disti...

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