Self-Assembly of Large DNA Origami with Custom-Designed Scaffolds

Chen, Xiaoxing; Wang, Qian; Jin, Peng; Long, Qipeng; Yu, Henry; Li, Zhe

doi:10.1021/acsami.8b09222

Cited by 36 publications

(27 citation statements)

References 34 publications

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“…To evaluate the generality of TALOS for application to a broad set of polyhedral geometries, we applied it generate the sequence design of all Platonic solids that have equal edge lengths, angles, and vertex junction numbers, as well as more complex geometries including Archimedean solids with unequal vertex angles, Johnson solids that include heterogeneity in vertex junction numbers, and Catalan solids that have unequal edge lengths (Figures S19–S31). Out of these 40 distinct geometric families, 28 (FV) and 32 (MV) DNA-NPs required scaffolds longer than the 7249-nt M13mp18 (Table S5), for which the remaining sequences were generated using 8064 nt, 8 recombinant phage sequences up to 31 274 nt, 58 or a random sequence.…”

Section: Resultsmentioning

confidence: 99%

Automated Sequence Design of 3D Polyhedral Wireframe DNA Origami with Honeycomb Edges

et al. 2019

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3D polyhedral wireframe DNA nanoparticles (DNA-NPs) fabricated using scaffolded DNA origami offer complete and independent control over NP size, structure, and asymmetric functionalization on the 10–100 nm scale. However, the complex DNA sequence design needed for the synthesis of these versatile DNA-NPs has limited their widespread use to date. While the automated sequence design algorithms DAEDALUS and vHelix-BSCOR apply to DNA-NPs synthesized using either uniformly dual or hybrid single-dual duplex edges, respectively, these DNA-NPs are relatively compliant mechanically and are therefore of limited utility for some applications. Further, these algorithms are incapable of handling DNA-NP edge designs composed of more than two duplexes, which are needed to enhance DNA-NP mechanical stiffness. As an alternative, here we introduce the scaffolded DNA origami sequence design algorithm TALOS, which is a generalized procedure for the fully automated design of wireframe 3D polyhedra composed of edges of any cross section with an even number of duplexes, and apply it to DNA-NPs composed uniformly of single honeycomb edges. We also introduce a multiway vertex design that enables the fabrication of DNA-NPs with arbitrary edge lengths and vertex angles and apply it to synthesize a highly asymmetric origami object. Sequence designs are demonstrated to fold robustly into target DNA-NP shapes with high folding efficiency and structural fidelity that is verified using single particle cryo-electron microscopy and 3D reconstruction. In order to test its generality, we apply TALOS to design an in silico library of over 200 DNA-NPs of distinct symmetries and sizes, and for broad impact, we also provide the software as open source for the generation of custom NP designs.

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Section: Resultsmentioning

confidence: 99%

Automated Sequence Design of 3D Polyhedral Wireframe DNA Origami with Honeycomb Edges

et al. 2019

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“…This scaffold was later used to assemble a 18 × 18 × 20 nm hollow 3D DNA origami box, which is a common DNA origami structure used as a potential drug delivery system [ 60 , 61 ]. This method, with the same helper phage, was also applied by Li’s group [ 62 ], who designed four different phagemids encoding four distinct ssDNA scaffolds, each greater than 10,000 nts. After purification, these scaffolds were folded into multiple large 2D DNA origami nanostructures with edge sizes up to 300 nm.…”

Section: Current Methods For Ssdna Scaffold Productionmentioning

confidence: 99%

Synthesis of DNA Origami Scaffolds: Current and Emerging Strategies

et al. 2020

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DNA origami nanocarriers have emerged as a promising tool for many biomedical applications, such as biosensing, targeted drug delivery, and cancer immunotherapy. These highly programmable nanoarchitectures are assembled into any shape or size with nanoscale precision by folding a single-stranded DNA scaffold with short complementary oligonucleotides. The standard scaffold strand used to fold DNA origami nanocarriers is usually the M13mp18 bacteriophage’s circular single-stranded DNA genome with limited design flexibility in terms of the sequence and size of the final objects. However, with the recent progress in automated DNA origami design—allowing for increasing structural complexity—and the growing number of applications, the need for scalable methods to produce custom scaffolds has become crucial to overcome the limitations of traditional methods for scaffold production. Improved scaffold synthesis strategies will help to broaden the use of DNA origami for more biomedical applications. To this end, several techniques have been developed in recent years for the scalable synthesis of single stranded DNA scaffolds with custom lengths and sequences. This review focuses on these methods and the progress that has been made to address the challenges confronting custom scaffold production for large-scale DNA origami assembly.

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“…In research by Shin and co‐workers, double‐stranded (ds) DNA could be employed as a scaffold to construct two discrete nanoscale objects . Li and co‐workers prepared four long single‐stranded DNA with sequences of 10 563, 10 782, 21 261, and 31 274 nucleotides to be used as scaffolds to construct larger DNA origami nanostructures …”

Section: Evolution Of Dna Origami Nanotechnologymentioning

confidence: 99%

“…[18] Li and co-workersp repared four long single-stranded DNA with sequences of 10 563,1 0782, 21 261, and 31 274 nucleotides to be used as scaffolds to construct larger DNA origami nanostructures. [19] In addition to the classical DNA-templated scaffold, RNA transcripts can also be employeda sR NA scaffolds to build RNA-DNAh ybrid origami. The group of Sugiyama successfully fabricateds even-helixb undled rectangular structures and sixhelix bundledt ubular structures by using RNA transcripts as scaffoldsa nd DNA sequences as staple strands.…”

Section: Development Of Dna Origami Nanotechnologymentioning

confidence: 99%

Multifunctional DNA Origami Nanoplatforms for Drug Delivery

et al. 2019

Chemistry An Asian Journal

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DNA nanotechnology has been employed in the construction of self‐assembled nano‐biomaterials with uniform size and shape for various biological applications, such as bioimaging, diagnosis, or therapeutics. Herein, recent successful efforts to utilize multifunctional DNA origami nanoplatforms as drug‐delivery vehicles are reviewed. Diagnostic and therapeutic strategies based on gold nanorods, chemotherapeutic drugs, cytosine–phosphate–guanine, functional proteins, gene drugs, and their combinations for optoacoustic imaging, photothermal therapy, chemotherapy, immunological therapy, gene therapy, and coagulation‐based therapy are summarized. The challenges and opportunities for DNA‐based nanocarriers for biological applications are also discussed.

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Self-Assembly of Large DNA Origami with Custom-Designed Scaffolds

Cited by 36 publications

References 34 publications

Automated Sequence Design of 3D Polyhedral Wireframe DNA Origami with Honeycomb Edges

Automated Sequence Design of 3D Polyhedral Wireframe DNA Origami with Honeycomb Edges

Synthesis of DNA Origami Scaffolds: Current and Emerging Strategies

Multifunctional DNA Origami Nanoplatforms for Drug Delivery

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