Abstract:Expanding the number of nucleotides in DNA increases the information density of functional DNA molecules, creating nanoassemblies that cannot be invaded by natural DNA/RNA in complex biological systems. Here, we show how six‐letter GACTZP DNA contributes this property in two parts of a nanoassembly: 1) in an aptamer evolved from a six‐letter DNA library to selectively bind liver cancer cells; and 2) in a six‐letter self‐assembling GACTZP nanotrain that carries the drug doxorubicin. The aptamer‐nanotrain assemb… Show more
Section: Applications Of Artificial Nucleobases In Molecular Medicinementioning
confidence: 99%
“…Based on artificially expanded genetic information systems, Benner's team and Tan's team produced a six‐letter aptamer (G,A,C,T,Z,P nucleotides) that selectively bind liver cancer cells. [ 128 ] As shown in Figure 10D, this six‐letter GACTZP aptamer served as a trigger to hybridize with the toehold of a DNA hairpin structure, thus generating an aptamer‐nanotrain assembly. This aptamer‐ nanotrain assembly can be used to charge with doxorubicin and killed cancer cells selectively.…”
Section: Applications Of Artificial Nucleobases In Molecular Medicinementioning
Comprehensive Summary
Nucleic acids are the hereditary information storage medium of life. Due to its high programmability and good biocompatibility, the applications of nucleic acids are not limited to their natural function. However, the efficiency of nucleic acids is often hampered by inherent limitations in numerous practical applications, including limited access to complex functional patterns due to only four building blocks, facile degradation by nucleases, rapid renal clearance, poor pharmacokinetic properties, and so on. To end this, the researchers developed unnatural base pairs (UBPs) and numerous artificial analogues of nucleosides and oligonucleotides in recent decades. The developed UBPs and nucleoside base analogues together constitute artificial nucleobase compilation, which promotes the development of biomedical sciences. Here, we describe the development of artificial nucleobase compilation and summarized its applications in precise molecular medicine, including PCR‐based diagnostics, aptamer‐based diagnostics, nucleobase analogue drugs construction, ASO modification, aptamer‐based therapeutics and biomaterials construction. This review provides an overview of current opportunities and challenges of artificial nucleobase‐related precise molecular medicine.
Section: Applications Of Artificial Nucleobases In Molecular Medicinementioning
confidence: 99%
“…Based on artificially expanded genetic information systems, Benner's team and Tan's team produced a six‐letter aptamer (G,A,C,T,Z,P nucleotides) that selectively bind liver cancer cells. [ 128 ] As shown in Figure 10D, this six‐letter GACTZP aptamer served as a trigger to hybridize with the toehold of a DNA hairpin structure, thus generating an aptamer‐nanotrain assembly. This aptamer‐ nanotrain assembly can be used to charge with doxorubicin and killed cancer cells selectively.…”
Section: Applications Of Artificial Nucleobases In Molecular Medicinementioning
Comprehensive Summary
Nucleic acids are the hereditary information storage medium of life. Due to its high programmability and good biocompatibility, the applications of nucleic acids are not limited to their natural function. However, the efficiency of nucleic acids is often hampered by inherent limitations in numerous practical applications, including limited access to complex functional patterns due to only four building blocks, facile degradation by nucleases, rapid renal clearance, poor pharmacokinetic properties, and so on. To end this, the researchers developed unnatural base pairs (UBPs) and numerous artificial analogues of nucleosides and oligonucleotides in recent decades. The developed UBPs and nucleoside base analogues together constitute artificial nucleobase compilation, which promotes the development of biomedical sciences. Here, we describe the development of artificial nucleobase compilation and summarized its applications in precise molecular medicine, including PCR‐based diagnostics, aptamer‐based diagnostics, nucleobase analogue drugs construction, ASO modification, aptamer‐based therapeutics and biomaterials construction. This review provides an overview of current opportunities and challenges of artificial nucleobase‐related precise molecular medicine.
“…Zhao and co‐workers and Tan and co‐workers reported using DNA aptamers to achieve high precise tumor cell drug delivery. [ 76–78 ] Besides, through covalently attaching the antibody on DNA nanostructures, it could mediate the specific binding between DNA nanostructures and proteins on cell membranes. A typical example is a logic‐gated nanorobot presented by Church and co‐workers in 2012, which was capable of responding to stimuli and transporting molecular payloads to cells.…”
Section: Dna Nanostructures On Cell Membranes/synthetic Lipid Bilayermentioning
Materials that can regulate the composition and structure of the cell membrane to fabricate engineered cells with defined functions are in high demand. Compared with other biomolecules, DNA has unique advantages in cell membrane engineering due to its excellent programmability and biocompatibility. Especially, the near‐atomic scale precision of DNA nanostructures facilitates the investigation of structure–property relations on the cell membrane. In this review, first the state of the art of functional DNA nanostructures is summarized, and then the overview of the use of DNA nanostructures to engineer the cell membrane is presented. Subsequently, applications of DNA nanostructures in modifying cell membrane morphology, controlling ions transport, and synthesizing high precise liposomes are highlighted. Finally, the challenges and outlook on using DNA nanostructures for cell membrane engineering are discussed.
“…( [63] 。如今，基于 DNA 分子修饰与组 装的细胞表面工程 [64][65][66] 已被用于细胞表面生物传感 [46,67,68] ，并显示出潜在的临 床应用价值 [69,70] 。 图 2 isRTA 策略用于膜蛋白标记与原位高灵敏成像和定量分析。分析过程包括：核酸探针及 引物(aptamer probe, AP)的 原位标记，DNA 滚环扩增(RCA) ，以及基于 RCA 的二次信号 放大(RTA) [42] 。 Figure 2 isRTA strategy for the label and ultra-sensitive quantification and imaging of membrane proteins, including in situ labeling to selectively assign an aptamer−primer probe (AP) to target PMP, the first (RCA) and second (RTA) rounds of isothermal amplification reactions, initiated by AP, to give enhanced quantitative signals [42] . (e) Flow cytometry analysis of the cell viability and encapsulation efficiency [63] .…”
Nature has presented multi-scale, multi-level, and multi-functionally assembled systems during evolution, from single-cell to the higher organisms of multi-cell systems. In the course of both physiological and disease processes, cells carry out a series of molecular events at their surface to promote intracellular communication, thus driving cell proliferation, differentiation and migration. A collection of these interacted cells of different types can help to construct a living system with complete functions. Therefore, the development of molecular modification and assembly technologies at cell surface is the key to explore cell interfacial behavior at the molecular level, which may help to understand interfacial molecular events and biochemical reactions. Meanwhile, molecular modification and assembly technologies can greatly promote the advance of many research and application fields, including biosensing, disease diagnosis, translational medicine, and tissue engineering. Therefore, this review will present the latest research progress, so as to systematically describe the use of molecular probes and assembled materials at cell surface, such as DNA and peptides, and thus give an outlook on their prospects for analytical applications.
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