DNA Origami. Группа авторов

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Figure 1.14 (a) DNA origami channel structure. Tubular pores (dark gray), main body (light gray), cholesterol moieties (gray) at the bottom of the main body, and TEM image. (b) The DNA channel is bound to the lipid bilayer membrane via cholesterol, and the pore domain penetrates the lipid membrane. TEM image of origami channels bound to a liposome.

      Source: Langecker et al. [103]/with permission of Springer Nature.

      (c) Precise control of liposome size using DNA origami templates. DNA‐DOPE conjugates were placed inside the ring via hybridization, then extra lipid was supplied, and the formed vesicle was dialyzed. Finally, the size‐controlled liposome was released from the ring template. (d) TEM images of size‐controlled liposomes.

      Source: Yang et al. [104]/with permission of Springer Nature.

Figure 1.15 Delivery of DNA origami structures to cells and functional control. (a) The prepared DNA origami structure is intercalated with the anticancer drug doxorubicin (Dox) and introduced into the cells.

      Source: Jiang et al. [108]/with permission of American Chemical Society.

      (b) Control the binding amount and release rate of Dox using DNA origami structures with different pitches (10.5 and 12 base pairs).

      Source: Zhao et al. [109].

      (c) Retention of DNA nanodevice in mouse (after two hours). Left: No coating. Accumulated in the bladder. Right: With coating. Distributed throughout the body.

      Source: Perrault and Shih [110].

      (d) Coating of the structure with PEG‐conjugated cationic polymer (polylysine K10‐PEG5K).

      Source: Ponnuswamy et al. [111]/Springer Nature/CC BY 4.0.

      In addition, tumor growth was suppressed by incorporating siRNA into the DNA origami structure [113]. A DNA origami structure carrying Bcl2 siRNA that suppresses apoptosis was prepared and introduced into the host cells. Using this structure, Bcl2 expression was suppressed by RNA interference resulting in suppression of tumor growth.

      1.13.2 Drug Release Using the Properties Characteristic for DNA Origami

      The twist of the bundled double‐helices can be controlled by changing the pitches which can be adjusted by the number of base‐pairs between crossovers [29]. Högberg and coworkers developed a drug delivery system using a pitch‐controlled 3D origami with Dox (Figure 1.15b) [109]. The 3D origami structure was designed using double helices with different pitches. By designing the DNA origami structures with a pitch of the usual 10.5 base pairs and a looser one of 12 base pairs, the amount of Dox binding to the loose structure increased by 33% compared with the usual type. The amount of incorporated drug can be adjusted, and it can be released slowly over time. The drug was efficiently taken up into cells, confirming that the DNA origami structure is effective for the efficient delivery of Dox. The structure was retained in the cells and apoptosis of cancer cells was effectively induced. This study shows the characteristics of DNA origami that can regulate drug release by designing the structure using different degrees of twist.

      1.13.3 DNA Origami Structures Coated with Lipids and Polymers

      To use a DNA origami structure in vivo, the instability of the DNA structure and the activation of the immune system are obstacles to further application. Therefore, it is necessary to suppress both degradation of the DNA structure against the nuclease and the suppression of immune activation in vivo. Natural biological particles such as viruses have a mechanism to avoid immune recognition during infection by covering the structure with lipids.

      Shih and coworker prepared an octahedral frame‐type DNA origami (c. 50 nm in diameter) covered with a lipid bilayer to prevent degradation and circulate in the blood stream of mice (Figure 1.15c) [110]. By coating with a PEG (polyethylene glycol)‐modified lipid bilayer, the DNA origami device showed resistance to degradation by nucleases. Immune activation was significantly reduced compared to uncoated structures. When these structures were injected into mice, the noncoated DNA origami was rapidly excreted (half‐life = 38 minutes), whereas the lipid‐coated DNA origami was retained for much longer (half‐life = 370 minutes). Furthermore, the researchers confirmed that the DNA origami structures were stable in low salt concentrations and in the medium by covering a barrel‐shaped DNA origami structure with cationic polymers (Figure 1.15d) [111]. In particular, it was found that by covering with a PEG‐conjugated cationic polymer, the DNA origami structure can stably exist in the body of a mouse up to 24 hours. In this way, by establishing a method suitable for biological applications, a medically applicable DNA nanodevices have also been developed.

      1.13.4 Nanorobot with Dynamic Mechanism

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