DNA Aptamers for Functionalisation of DNA Origami Nanostructures

Sakai, Yusuke; Islam, Md. Sirajul; Adamiak, Martyna; Shiu, Simon Chi‐Chin; Tanner, Julian A.; Heddle, Jonathan G.

doi:10.20944/preprints201810.0204.v1

Cited by 4 publications

(1 citation statement)

References 81 publications

(99 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cholesterol tags or other membranes-selective moieties may be used as a route to target functional DNA or RNA cargo towards immune cells thereby complementing aptamerbased recognition. 72 Vaccine development could benefit from this selective interaction as nucleic acid vaccines have to be taken up by immune cells to translate the genetic information into a protein that elicits the immune response. Cholesterol-mediated binding may also be a general basis to assist targeting other biomedically relevant substances to immune cells, especially for immunomodulation.…”

Section: Discussionmentioning

confidence: 99%

DNA Nanodevices with Selective Immune Cell Interaction and Function

et al. 2021

View full text Add to dashboard Cite

DNA nanotechnology produces precision nanostructures of defined chemistry. Expanding their use in biomedicine requires designed biomolecular interaction and function. Of topical interest are DNA nanostructures that function as vaccines with potential advantages over non-structured nucleic acids in terms of serum stability and selective interaction with primary human immune cells. Here we describe how compact DNA nanobarrels bind with a 400-fold selectivity via membrane anchors to white blood immune cells over erythrocytes, without affecting cell viability.The selectivity is based on the preference of the cholesterol lipid anchor for the more fluid immune cell membranes compared to the lower membrane fluidity of erythrocytes. Compacting DNA into the nanostructures also gives rise to increased serum stability. The DNA barrels furthermore functionally modulate white blood cells by suppressing the immune response to pro-inflammatory endotoxin lipopolysaccharide. This is likely due to electrostatic or steric blocking of toll-like receptors on white blood cells. Our findings on immune-cell specific DNA nanostructures may be applied for vaccine development, immunomodulatory therapy to suppress septic shock, or the targeting of bioactive substances to immune cells. KEYWORDS DNA; DNA nanotechnology, bilayer membrane, white blood cells, lipids, immunomodulation, nanostructures ToC GRAPHIC 3 DNA nanostructures advance nanotechnology and the life sciences. Compared to other materials, DNA nanostructures have an unsurpassed highly controllable architecture which is based on predictable folding using base-pairing rules. [1][2][3][4][5] By exploiting these properties, the functional structures are increasingly designed to benefit areas outside DNA nanotechnology. Examples include DNA scaffolds which precisely position proteins and other biomolecular components for biophysical and molecular biological research, [1][2][6][7][8] or as scaffold to organize enzymes into efficient multistep biocatysts. 9 Furthermore, predictable changes in DNA nanostructures have been exploited for smart biosensing 10 to measure pH inside cells [10][11][12] or to delivery bioactive cargo into cells. 13 The greatest reward is expected in biomedicine [14][15][16] as illustrated by a DNA nanorobot to deliver anti-cancer drugs 17 or larger nanostructures that mitigate acute kidney injury within animal models. [18][19] Immunology and vaccine development are of topical interests for DNA nanotechnology. Nonstructured DNA and RNA have previously been developed into vaccines against cancer. [20][21][22][23] The relevance of nucleic acids-based therapy platforms has been further increased with the SARS-CoV-2 pandemic. 24-29 A main advantage of mRNA type vaccines is the speed at which they can be developed and manufactured compared to traditional protein-based vaccines. Nevertheless, DNA and RNA vaccines have disadvantages including their low potency, poor uptake into immune cells, lack of stability against nucleases, and fast clearance rates. 20,30-31 These la...

show abstract

Section: Discussionmentioning

confidence: 99%

DNA Nanodevices with Selective Immune Cell Interaction and Function

et al. 2021

View full text Add to dashboard Cite

show abstract

3D RNA-scaffolded wireframe origami

Parsons

Allan

et al. 2022

Preprint

View full text Add to dashboard Cite

Hybrid RNA:DNA origami, in which a long RNA scaffold strand is folded into a target nanostructure via thermal annealing with complementary DNA oligos, has only been explored to a limited extent despite its unique potential for biomedical delivery of mRNA, tertiary structure characterization of long RNAs, and fabrication of artificial ribozymes. Here, we investigate design principles of wireframe RNA-scaffolded origami in three dimensions rendered as polyhedra composed of dual-duplex edges. We computationally designed, fabricated, and characterized tetrahedra folded from an EGFP-encoding messenger RNA and de Bruijn sequences, an octahedron folded with M13 transcript RNA, and an octahedron and pentagonal bipyramids folded with 23S ribosomal RNA, demonstrating the ability to make diverse polyhedral shapes with distinct structural and functional RNA scaffolds. We characterized secondary and tertiary structures using dimethyl sulfate mutational profiling and cryo-electron microscopy, revealing for the first time insight into both global and local, base-level structures of origami. Our top-down sequence design strategy enables the use of long RNAs as functional scaffolds for complex wireframe origami.

show abstract

Obtaining Precise Molecular Information via DNA Nanotechnology

Tang

Han

2021

Membranes

View full text Add to dashboard Cite

Precise characterization of biomolecular information such as molecular structures or intermolecular interactions provides essential mechanistic insights into the understanding of biochemical processes. As the resolution of imaging-based measurement techniques improves, so does the quantity of molecular information obtained using these methodologies. DNA (deoxyribonucleic acid) molecule have been used to build a variety of structures and dynamic devices on the nanoscale over the past 20 years, which has provided an accessible platform to manipulate molecules and resolve molecular information with unprecedented precision. In this review, we summarize recent progress related to obtaining precise molecular information using DNA nanotechnology. After a brief introduction to the development and features of structural and dynamic DNA nanotechnology, we outline some of the promising applications of DNA nanotechnology in structural biochemistry and in molecular biophysics. In particular, we highlight the use of DNA nanotechnology in determination of protein structures, protein–protein interactions, and molecular force.

show abstract

DNA Aptamers for Functionalisation of DNA Origami Nanostructures

Cited by 4 publications

References 81 publications

DNA Nanodevices with Selective Immune Cell Interaction and Function

DNA Nanodevices with Selective Immune Cell Interaction and Function

3D RNA-scaffolded wireframe origami

Obtaining Precise Molecular Information via DNA Nanotechnology

Contact Info

Product

Resources

About