Evolution of a highly functional circular DNA aptamer in serum

Mao, Yu; Gu, Jimmy; Chang, Dingran; Wang, Lei; Yao, Lili; Ma, Qihui; Z, Luo; Qu, Hao; Li, Yingfu; Zheng, Lei

doi:10.1093/nar/gkaa800

Cited by 31 publications

(16 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the present study, we proposed a CiD agonist strategy in which circularized DNA aptamers are used to screen for optimal ligand geometry to induce a desired receptor activation level. While aptamer circularization has previously been adopted to construct bispecific aptamers or to improve exonuclease resistance, [37][38][39][40][41] the current study utilized it for the control of the distance between two aptamers at nanometer-scale, as well as their relative orientation. As a proof-of-concept study, we targeted Met and identified two partial Met agonists, C12 and C22, exhibiting reduced maximal Met activation potentials compared to that of HGF.…”

Section: Discussionmentioning

confidence: 99%

CiD agonists: Circular DNA-based agonists for the fine-tuning of receptor signaling

Ueki

Watanabe

Akiyama

et al. 2022

Preprint

View full text Add to dashboard Cite

Receptor dimerization geometry plays a significant role in signal transduction induced by growth factors and cytokines. A chemical strategy capable of controlling dimerization geometry provides a means for studying receptor activation mechanisms and designing novel agonists transducing fine-tuned receptor signaling. However, a generalized approach that can be applied to given receptors is still limited. In the present study, we propose a strategy using CiD agonists (circular DNA aptamer-based agonists), where circularized DNA is used as a rigid scaffold to present two receptor-binding aptamers from the duplex linker domain in a fixed distance and orientation. We targeted Met, a receptor for hepatocyte growth factor (HGF), and designed Met-binding CiD agonists with variable linker length. The designed CiD agonists demonstrated a distinctive periodic change in the receptor activation potential dependent on their linker length. This strategy represents a useful approach for the rational design of partial agonists that transduce fine-tuned receptor signaling and exert moderate biological activity.

show abstract

Section: Discussionmentioning

confidence: 99%

CiD agonists: Circular DNA-based agonists for the fine-tuning of receptor signaling

Ueki

Watanabe

Akiyama

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Currently, several groups are investigating ways to improve upon the aptamer’s half-life and renal clearance. Circular DNA aptamers can overcome some of these challenges [ 55 , 138 ]. New circular DNA aptamer CTBA4T-B1, binds to exosite 1 of thrombin.…”

Section: Discussionmentioning

confidence: 99%

“…New circular DNA aptamer CTBA4T-B1, binds to exosite 1 of thrombin. This aptamer is a potent anticoagulant, binds with a high affinity to thrombin, and most importantly, it has a half-life of approximately 8 h in the human serum [ 138 ]. Other ways to improve the half-life have been investigated as well, including adding modified bases [ 32 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Overview of the Therapeutic Potential of Aptamers Targeting Coagulation Factors

Liu

Zaman

Fortenberry

2021

IJMS

View full text Add to dashboard Cite

Aptamers are single-stranded DNA or RNA sequences that bind target molecules with high specificity and affinity. Aptamers exhibit several notable advantages over protein-based therapeutics. Aptamers are non-immunogenic, easier to synthesize and modify, and can bind targets with greater affinity. Due to these benefits, aptamers are considered a promising therapeutic candidate to treat various conditions, including hematological disorders and cancer. An active area of research involves developing aptamers to target blood coagulation factors. These aptamers have the potential to treat cardiovascular diseases, blood disorders, and cancers. Although no aptamers targeting blood coagulation factors have been approved for clinical use, several aptamers have been evaluated in clinical trials and many more have demonstrated encouraging preclinical results. This review summarized our knowledge of the aptamers targeting proteins involved in coagulation, anticoagulation, fibrinolysis, their extensive applications as therapeutics and diagnostics tools, and the challenges they face for advancing to clinical use.

show abstract

“…We proved that by using CircLigase-premade circular DNAs as certain starting components, topological DNA rings, especially those with higher-order complexity, can be synthesized with considerably elevated quantity and quality. Besides the potential applications in DNA nanotechnology, programmed CircLigase with robust circularization activity could offer circular ssDNA libraries with less sequence bias, possibly leading us to thoroughly select circular aptamers with enhanced stability for cancer diagnosis and therapy. ,− Last but not the least, because of CircLigase’s nature of being a RNA ligase and the chemical similarity between DNA and RNA, the terminal hybridization strategy developed on DNA should also work on RNA, allowing us to program CircLigase to robustly synthesize those naturally existing circular RNAs − in vitro for their structural and functional studies.…”

Section: Discussionmentioning

confidence: 99%

Programming CircLigase Catalysis for DNA Rings and Topologies

Zhang

et al. 2020

Anal. Chem.

View full text Add to dashboard Cite

Circular single-stranded (ss) DNA is an essential element in rolling circle amplification and many DNA nanotechnology constructions. It is commonly synthesized from linear ssDNA by a ligase, which nevertheless suffers from low and inconsistent efficiency due to the simultaneous formation of concatemeric byproducts. Here, we design an intramolecular terminal hybridization strategy to program the ring formation catalytic process of CircLigase, a thermostable RNA ligase 1 that can ligate ssDNA in an intramolecular fashion. With the enthalpy gained from the programmed hybridization to override disfavored entropic factors associated with end coupling, we broke the limit of natural CircLigase on circularization of ssDNA, realizing over 75% yields of byproduct-free monomeric rings on a series of hundred-to-half-kilo-based linear DNAs. We found that this hybridization strategy can be twisted from intra- to intermolecular to also program CircLigase to efficiently and predominantly join one ssDNA strand to another. We focused on DNA rings premade by CircLigase and demonstrated their utility in elevating the preparation, quantity, and quality of DNA topologies. We expect that the new insights on engineering CircLigase will further promote the development of nucleic acid biotechnology and nanotechnology.

show abstract

Evolution of a highly functional circular DNA aptamer in serum

Cited by 31 publications

References 50 publications

CiD agonists: Circular DNA-based agonists for the fine-tuning of receptor signaling

CiD agonists: Circular DNA-based agonists for the fine-tuning of receptor signaling

Overview of the Therapeutic Potential of Aptamers Targeting Coagulation Factors

Programming CircLigase Catalysis for DNA Rings and Topologies

Contact Info

Product

Resources

About