Aptamers against Cells Overexpressing Glypican 3 from Expanded Genetic Systems Combined with Cell Engineering and Laboratory Evolution

Zhang, Liqin; Yang, Zunyi; Trinh, Thu Le; Teng, I-Ting; Wang, Qianqian; Bradley, Kevin M.; Hoshika, Shuichi; Wu, Qiang-Sheng; Cansız, Sena; Rowold, Diane J.; McLendon, Chris; Kim, Myong-Sang; Wu, Yuan; Cui, Cheng; Liu, Yuan; Hou, Weijia; Stewart, Kimberly; Wan, Shuo; Liu, Chen; Benner, Steven A.; Tan, Weihong

doi:10.1002/ange.201605058

Cited by 14 publications

(7 citation statements)

References 32 publications

(14 reference statements)

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“…The additional four nucleotides form two pairs (the P : Z and B : S pairs) with the same size and shape as the natural A:T and G:C pairs. Subsets of hachimoji DNA have been built into signaling beacons that avoid invasion by natural DNA, translation systems to encode additional amino acids, diagnostics products, and laboratory in vitro evolution (LIVE) platforms that create aptamers with additional nucleotides that bind to cells and proteins …”

Section: Figurementioning

confidence: 99%

“…We first asked whether GACT ZP repeats placed in a nanotrain could bind doxorubicin. Here, a series of GACT ZP oligonucleotides were designed from a report that a single unit of duplex GCA/CGT or CGA/GCT can intercalate one molecule of doxorubicin . The designed sequences were self‐complementary, forming eight consecutive GCA/CGT, GC Z /CG P , or PZ A/ ZP T paired units.…”

Section: Figurementioning

confidence: 99%

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An Aptamer‐Nanotrain Assembled from Six‐Letter DNA Delivers Doxorubicin Selectively to Liver Cancer Cells

et al. 2019

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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 assembly, charged with doxorubicin, selectively kills liver cancer cells in culture, as the selectivity of the aptamer binding directs doxorubicin into the aptamer‐targeted cells. The assembly does not kill untransformed cells that the aptamer does not bind. This architecture, built with an expanded genetic alphabet, is reminiscent of antibodies conjugated to drugs, which presumably act by this mechanism as well, but with the antibody replaced by an aptamer.

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

An Aptamer‐Nanotrain Assembled from Six‐Letter DNA Delivers Doxorubicin Selectively to Liver Cancer Cells

et al. 2019

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“…One example of xNA are artificially expanded genetic information systems (AEGIS) that increase the number of independently replicable nucleotides from 4 to as many as 12. By shuffling hydrogen bonding patterns of the G:C and A:T pairs while retaining their Watson-Crick sizecomplementarity [26], AEGIS DNA can evolve to produce molecules (AEGISbodies) that bind to liver and breast cancer cells [27], isolated proteins [28], and recombinant cell systems [27]. Several of these are used to deliver drugs to cells in AEGISbodynanotrain-drug conjugates [29].…”

Section: Introductionmentioning

confidence: 99%

Fluorinated oil-surfactant mixtures with the density of water: artificial cells for synthetic biology

Laos

Benner

2021

Preprint

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Water-in-oil emulsions provide matrices for compartments that have many uses in diversity science. However, hydrophobic species are frequently incompatible with biological systems. For this reason, fluorinated matrices are often sought, since fluorinated species are neither hydrophilic nor hydrophobic; they therefore do not interact with most biomolecules. However, most fluorinated oils have densities much higher than the density of water (1 g/ml). Consequently, water droplets float in fluorinated oils, aggregating near their surfaces. This facilitates droplet-droplet collision and fusion, exposing droplets to air interfaces and making their manipulation difficult. Here, we report the synthesis, characterization, and use of fluorinated polysiloxane oils that have densities close to the density of water. These, with a non-ionic fluorosilicone surfactant, produce thermostable water-in-oil emulsions that neither float nor sink. We show how droplets in these emulsions can host many biological processes, including PCR, DNA origami, rolling circle amplification (RCA), and Taqman ® assays. Further, oil-diffusible reagents can initiate reactions within the droplets. The droplets can also be used with unnatural DNA emerging from synthetic biology, including DNA built from artificially expanded genetic information systems (AEGIS) with six nucleotide "letters".

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“…Increased diversity is, for example, useful in the search for affinity binders like aptamers. Including an UBP in SELEX (systematic evolution of ligands by exponential enrichment) processes can be used to generate aptamers that bind to proteins and cells, as has already successfully been demonstrated . Apart from generating diversity in DNA and RNA, a third base pair can be used to incorporate non‐proteinogenic amino acids into a polypeptide chain by ribosome‐based translation.…”

Section: Introduction To Unnatural Base Pairsmentioning

confidence: 99%

The Structural Basis for Processing of Unnatural Base Pairs by DNA Polymerases

Marx

Betz

2020

Chemistry A European J

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Unnatural base pairs (UBPs) greatly increase the diversity of DNA and RNA, furthering their broad range of molecular biological and biotechnological approaches. Different candidates have been developed whereby alternative hydrogen‐bonding patterns and hydrophobic and packing interactions have turned out to be the most promising base‐pairing concepts to date. The key in many applications is the highly efficient and selective acceptance of artificial base pairs by DNA polymerases, which enables amplification of the modified DNA. In this Review, computational as well as experimental studies that were performed to characterize the pairing behavior of UBPs in free duplex DNA or bound to the active site of KlenTaq DNA polymerase are highlighted. The structural studies, on the one hand, elucidate how base pairs lacking hydrogen bonds are accepted by these enzymes and, on the other hand, highlight the influence of one or several consecutive UBPs on the structure of a DNA double helix. Understanding these concepts facilitates optimization of future UBPs for the manifold fields of applications.

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Aptamers against Cells Overexpressing Glypican 3 from Expanded Genetic Systems Combined with Cell Engineering and Laboratory Evolution

Cited by 14 publications

References 32 publications

An Aptamer‐Nanotrain Assembled from Six‐Letter DNA Delivers Doxorubicin Selectively to Liver Cancer Cells

An Aptamer‐Nanotrain Assembled from Six‐Letter DNA Delivers Doxorubicin Selectively to Liver Cancer Cells

Fluorinated oil-surfactant mixtures with the density of water: artificial cells for synthetic biology

The Structural Basis for Processing of Unnatural Base Pairs by DNA Polymerases

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