Enhanced Stability of DNA Nanostructures by Incorporation of Unnatural Base Pairs

ChemPhysChem ◽  
2017 ◽  
Vol 18 (21) ◽  
pp. 2977-2980 ◽  
Author(s):  
Qing Liu ◽  
Guocheng Liu ◽  
Ting Wang ◽  
Jing Fu ◽  
Rujiao Li ◽  
...  
Keyword(s):  
Dna Nanostructures ◽  
Base Pairs ◽  
Enhanced Stability

scholarly journals Nanobiomedicine: Protein Coating of DNA Nanostructures for Enhanced Stability and Immunocompatibility (Adv. Healthcare Mater. 18/2017)

2017 ◽  
Vol 6 (18) ◽  
Author(s):  
Henni Auvinen ◽  
Hongbo Zhang ◽  
Nonappa ◽  
Alisa Kopilow ◽  
Elina H. Niemelä ◽  
...  
Keyword(s):  
Dna Nanostructures ◽  
Protein Coating ◽  
Enhanced Stability

scholarly journals Regulation of 2D DNA Nanostructures by the Coupling of Tile Curvatures and Arm Twists

2021 ◽  
Author(s):  
Chuan Jiang ◽  
Biao Lu ◽  
Wei Zhang ◽  
Yoel P. Ohayon ◽  
Caihong Ni ◽  
...  
Keyword(s):  
Transverse Section ◽  
Regular Polygon ◽  
Holliday Junctions ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
Base Pairs ◽  
Left Handed ◽  
Different Types ◽  
Sticky End ◽  
Structural Descriptions

DNA overwinding and underwinding between adjacent Holliday junctions have been applied in DNA origami constructs to design both left-handed and right-handed nanostructures. For a variety of DNA tubes assembled from small tiles, only a theoretical approach of the intrinsic tile curvature was previously used to explain their formation. Details regarding the quantitative and structural descriptions of the intrinsic tile curvature and its evolution in DNA tubes by coupling with arm twists were missing. In this work, we designed three types of tile cores from a circular 128 nucleotide scaffold by longitudinal weaving (LW), bridging longitudinal weaving (bLW), and transverse weaving (TW) and assembled their 2D planar or tubular nanostructures via inter-tile arms with a distance of an odd or even number of DNA half-turns. The biotin/streptavidin (SA) labeling technique was applied to define the tube configuration with addressable inside and outside surfaces and thus their component tile conformation with addressable concave and convex curvatures. Both chiral tubes possessing left-handed and right-handed curvatures could be generated by finely tuning p and q in bLW-E<sub>p/q</sub> designs (bLW tile cores joined together by inter-tile arms of an even number of half-turns with the arm length of p base pairs (bp) and the sticky end length of q nucleotides (nt)). We were able to assign the chiral indices (n,m) to each specific tube from the high-resolution AFM images, and thus estimated the tile curvature angle with a regular polygon model that approximates each tube’s transverse section. We attribute the curvature evolution of bLW-E<sub>p/q</sub> tubes composed of the same tile core to the coupling of the intrinsic tile curvature and different arm twists. A better understanding of the integrated actions of different types of twisting forces on DNA tubes will be much more helpful in engineering DNA nanostructures in the future.

scholarly journals Unraveling the interaction between doxorubicin and DNA origami nanostructures for customizable chemotherapeutic drug release

2020 ◽  
Author(s):  
Heini Ijäs ◽  
Boxuan Shen ◽  
Amelie Heuer-Jungemann ◽  
Adrian Keller ◽  
Mauri A. Kostiainen ◽  
...  
Keyword(s):  
Drug Release ◽  
Targeted Delivery ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
Base Pairs ◽  
Experimental Conditions ◽  
Spectral Changes ◽  
Dna Binding Affinity ◽  
2D And 3D ◽  
Release Profiles

ABSTRACTDoxorubicin (DOX) is a common drug in cancer chemotherapy, and its high DNA-binding affinity can be harnessed in preparing DOX-loaded DNA nanostructures for targeted delivery and therapeutics. Although DOX has been widely studied, the existing literature of DOX-loaded DNA nanocarriers remains limited and incoherent. Here, based on an in-depth spectroscopic analysis, we characterize and optimize the DOX loading into different 2D and 3D scaffolded DNA origami nanostructures (DONs). In our experimental conditions, all DONs show similar DOX binding capacities (one DOX molecule per two to three base pairs), and the binding equilibrium is reached within seconds, remarkably faster than previously acknowledged. To characterize customizable drug release profiles, DON degradation and DOX release from the complexes upon DNase I digestion was studied. For the employed DONs, the relative doses (DOX molecules released per unit time) may vary by two orders of magnitude depending on the DON superstructure. In addition, we identify DOX aggregation mechanisms and spectral changes linked to pH, magnesium, and DOX concentration. This has been largely ignored in experimenting with DNA nanostructures, but is probably a major source of the incoherence of the experimental results so far. Therefore, we believe this work can act as a guide to tailoring the release profiles and developing better drug delivery systems based on DNA carriers.

scholarly journals Protein Coating of DNA Nanostructures for Enhanced Stability and Immunocompatibility

2017 ◽  
Vol 6 (18) ◽  
pp. 1700692 ◽  
Author(s):  
Henni Auvinen ◽  
Hongbo Zhang ◽  
Nonappa ◽  
Alisa Kopilow ◽  
Elina H. Niemelä ◽  
...  
Keyword(s):  
Dna Nanostructures ◽  
Protein Coating ◽  
Enhanced Stability

scholarly journals Regulation of 2D DNA Nanostructures by the Coupling of Tile Cur-Vatures and Arm Twists

2021 ◽  
Author(s):  
Chuan Jiang ◽  
Biao Lu ◽  
Wei Zhang ◽  
Yoel P. Ohayon ◽  
Caihong Ni ◽  
...  
Keyword(s):  
Transverse Section ◽  
Regular Polygon ◽  
Holliday Junctions ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
Base Pairs ◽  
Left Handed ◽  
Different Types ◽  
Sticky End ◽  
Structural Descriptions

DNA overwinding and underwinding between adjacent Holliday junctions have been applied in DNA origami constructs to design both left-handed and right-handed nanostructures. For a variety of DNA tubes assembled from small tiles, only an abstract concept of the intrinsic tile curvature was previously used to explain their formation. Details regarding the quantitative and structural descriptions of the intrinsic tile curvature and its evolution in DNA tubes by coupling with arm twists have been lacking. In this work, we designed three types of tile cores from a circular 128 nucleotide scaffold by longitudinal weaving (LW), bridging longitudinal weaving (bLW), and transverse weaving (TW) and assembled their 2D planar or tubular nanostructures via inter-tile arms with a distance of an odd or even number of DNA half-turns. The biotin/streptavidin (SA) labeling technique was applied to define the tube configuration with addressable inside and outside surfaces and thus their component tile conformation with addressable concave and convex curvatures. Both chiral tubes possessing left-handed and right-handed curvatures could be generated by finely tuning p and q in bLW-E<sub>p/q</sub> designs (bLW tile cores joined together by inter-tile arms of even number of half-turns with the arm length of p base pairs (bp) and the sticky end length of q nucleotides (nt)). We were able to assign the chiral indices (n,m) to each specific tube from the high-resolution AFM images, and thus estimated the tile curvature angle with a regular polygon model that approximates each tube’s transverse section. We attribute the curvature evolution of bLW-E<sub>p/q</sub> tubes composed of the same tile core to the coupling of the intrinsic tile curvature and different arm twists. A better understanding of integrated actions of different types of twisting forces on DNA tubes will be much more helpful in engineering DNA nanostructures in the future.

scholarly journals Regulation of 2D DNA Nanostructures by the Coupling of Tile Cur-Vatures and Arm Twists

2021 ◽  
Author(s):  
Chuan Jiang ◽  
Biao Lu ◽  
Wei Zhang ◽  
Yoel P. Ohayon ◽  
Caihong Ni ◽  
...  
Keyword(s):  
Transverse Section ◽  
Regular Polygon ◽  
Holliday Junctions ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
Base Pairs ◽  
Left Handed ◽  
Different Types ◽  
Sticky End ◽  
Structural Descriptions

DNA overwinding and underwinding between adjacent Holliday junctions have been applied in DNA origami constructs to design both left-handed and right-handed nanostructures. For a variety of DNA tubes assembled from small tiles, only an abstract concept of the intrinsic tile curvature was previously used to explain their formation. Details regarding the quantitative and structural descriptions of the intrinsic tile curvature and its evolution in DNA tubes by coupling with arm twists have been lacking. In this work, we designed three types of tile cores from a circular 128 nucleotide scaffold by longitudinal weaving (LW), bridging longitudinal weaving (bLW), and transverse weaving (TW) and assembled their 2D planar or tubular nanostructures via inter-tile arms with a distance of an odd or even number of DNA half-turns. The biotin/streptavidin (SA) labeling technique was applied to define the tube configuration with addressable inside and outside surfaces and thus their component tile conformation with addressable concave and convex curvatures. Both chiral tubes possessing left-handed and right-handed curvatures could be generated by finely tuning p and q in bLW-E<sub>p/q</sub> designs (bLW tile cores joined together by inter-tile arms of even number of half-turns with the arm length of p base pairs (bp) and the sticky end length of q nucleotides (nt)). We were able to assign the chiral indices (n,m) to each specific tube from the high-resolution AFM images, and thus estimated the tile curvature angle with a regular polygon model that approximates each tube’s transverse section. We attribute the curvature evolution of bLW-E<sub>p/q</sub> tubes composed of the same tile core to the coupling of the intrinsic tile curvature and different arm twists. A better understanding of integrated actions of different types of twisting forces on DNA tubes will be much more helpful in engineering DNA nanostructures in the future.

scholarly journals Membrane activity of a DNA-based ion channel depends on the stability of its double-stranded structure.

2021 ◽  
Author(s):  
Diana Morzy ◽  
Himanshu Joshi ◽  
Sarah E Sandler ◽  
Aleksei Aksimentiev ◽  
Ulrich F Keyser
Keyword(s):  
Ion Channels ◽  
Lipid Bilayer ◽  
Lipid Membranes ◽  
Degrees Of Freedom ◽  
Dna Nanotechnology ◽  
Md Simulations ◽  
Dna Nanostructures ◽  
Base Pairs ◽  
Dna Nanostructure ◽  
Synthetic Ion Channels

Structural DNA nanotechnology has emerged as a promising method for designing spontaneously-inserting and fully-controllable synthetic ion channels. However, both insertion efficiency and stability of existing DNA-based ion channels leave much room for improvement. Here, we demonstrate an approach to overcoming the unfavorable DNA-lipid interactions that hinder the formation of a stable transmembrane pore. Our all-atom MD simulations and experiments show that the insertion-driving cholesterol modifications, when introduced at an end of a DNA strand, are likely to cause fraying of the terminal base pairs as the DNA nanostructure adopts its energy-minimum configuration in the membrane. We also find that fraying of base pairs distorts nicked DNA constructs when embedded in a lipid bilayer. Here, we show that DNA nanostructures that do not have discontinuities (nicks) in their DNA backbones form considerably more stable DNA-induced conductive pores and insert into lipid membranes with a higher efficiency than the equivalent nicked constructs. Moreover, lack of nicks allows to design and maintain membrane-spanning helices in a tilted orientation within lipid bilayer. Thus, reducing the conformational degrees of freedom of the DNA nanostructures enables better control over their function as synthetic ion channels.

scholarly journals Unraveling the interaction between doxorubicin and DNA origami nanostructures for customizable chemotherapeutic drug release

2021 ◽  
Vol 49 (6) ◽  
pp. 3048-3062
Author(s):  
Heini Ijäs ◽  
Boxuan Shen ◽  
Amelie Heuer-Jungemann ◽  
Adrian Keller ◽  
Mauri A Kostiainen ◽  
...  
Keyword(s):  
Drug Release ◽  
Targeted Delivery ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
Base Pairs ◽  
Experimental Conditions ◽  
Dna Binding Affinity ◽  
2D And 3D ◽  
Release Profiles ◽  
Dna Carriers

Abstract Doxorubicin (DOX) is a common drug in cancer chemotherapy, and its high DNA-binding affinity can be harnessed in preparing DOX-loaded DNA nanostructures for targeted delivery and therapeutics. Although DOX has been widely studied, the existing literature of DOX-loaded DNA-carriers remains limited and incoherent. Here, based on an in-depth spectroscopic analysis, we characterize and optimize the DOX loading into different 2D and 3D scaffolded DNA origami nanostructures (DONs). In our experimental conditions, all DONs show similar DOX binding capacities (one DOX molecule per two to three base pairs), and the binding equilibrium is reached within seconds, remarkably faster than previously acknowledged. To characterize drug release profiles, DON degradation and DOX release from the complexes upon DNase I digestion was studied. For the employed DONs, the relative doses (DOX molecules released per unit time) may vary by two orders of magnitude depending on the DON superstructure. In addition, we identify DOX aggregation mechanisms and spectral changes linked to pH, magnesium, and DOX concentration. These features have been largely ignored in experimenting with DNA nanostructures, but are probably the major sources of the incoherence of the experimental results so far. Therefore, we believe this work can act as a guide to tailoring the release profiles and developing better drug delivery systems based on DNA-carriers.

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