Probing the Coagulation Pathway with Aptamers Identifies Combinations that Synergistically Inhibit Blood Clot Formation

Bompiani, Kristin M.; Lohrmann, Jens; Pitoc, George A.; Frederiksen, James W.; Mackensen, G. Burkhard; Sullenger, Bruce A.

doi:10.1016/j.chembiol.2014.05.016

Cited by 16 publications

(19 citation statements)

References 38 publications

(58 reference statements)

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“…Although no individual aptamer has yet rivalled heparin, a widely-used injectable anticoagulant 113 , a combination of multiple aptamers targeting different coagulation enzymes can be as potent as heparin for prevention of fibrin clot formation 114 . Unfortunately, a cocktail formulation of multiple aptamers significantly increases the complexity and cost of clinical development 115 .…”

Section: Recent Progress In Aptamer-based Therapeuticsmentioning

confidence: 99%

Aptamers as targeted therapeutics: current potential and challenges

Zhou

Rossi

2016

Nat Rev Drug Discov

1,600

1,316

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Nucleic acid aptamers, often termed “chemical antibodies”, are functionally comparable to traditional antibodies, but offer several advantages including their relatively small physical size, flexible structure, quick chemical production, versatile chemical modification, high stability, and lack of immunogenicity. In addition, many aptamers internalize upon binding to cellular receptors making them useful targeted delivery agents for siRNAs, microRNAs and conventional drugs. However,Ge several crucial factors, such as their inherent physicochemical characteristics and lack of safety data, have delayed the clinical translation of therapeutic aptamers. This review discusses these challenges, highlighting recent clinical developments and technological advances that have revived impetus for this promising class of therapeutics.

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Section: Recent Progress In Aptamer-based Therapeuticsmentioning

confidence: 99%

Aptamers as targeted therapeutics: current potential and challenges

Zhou

Rossi

2016

Nat Rev Drug Discov

1,600

1,316

View full text Add to dashboard Cite

show abstract

“…The improved half‐life of aptamers in vivo is suggestive of future clinical application as molecular imaging agents . Of note, aptamers themselves can be used as therapeutics in blood clotting, or local treatment, or inducing antitumor effect . Furthermore, aptamer‐mediated delivery systems have been broadly applied in cancer therapies, including aptamer‐drug conjugates, aptamer‐nanoparticle/polymer‐drug delivery system, and aptamer‐mediated cancer nucleic acid therapy .…”

Section: Aptamer Emerges As a Prominent Targeting Ligand For Nanodelimentioning

confidence: 99%

Exosomes and Nanoengineering: A Match Made for Precision Therapeutics

et al. 2019

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Intense efforts from both scientists and physicians across Australia have been devoted onward advancing studies to fill the gap in understanding the biology and pathogenesis underlying cancer development. Exosomes are membrane-bound bio-nanoparticles secreted or released by most cells into the extracellular space. There has been an increasing interest in such bio-nanoparticles over the past 10 years, evident from the publication number of only 324 papers in 2006 to a massive increase to 4603 publications in 2018 with the search term "exosome" based on title/abstract in PubMed. Among these studies, 151 articles published from 2007 to 2018 are from Australian institutions, with 33 papers published in 2018. Such a strong surge of interest is due to discoveries that exosomes play key roles in intercellular and intertissue communication mediated by virtue of cargos contained inside the membrane-confined space. Furthermore, exosome cargos, including proteins, mRNAs and miRNAs, are linked to the Targeted exosomal delivery systems for precision nanomedicine attract wide interest across areas of molecular cell biology, pharmaceutical sciences, and nanoengineering. Exosomes are naturally derived 50-150 nm nanovesicles that play important roles in cell-to-cell and/or cell-to-tissue communications and cross-species communication. Exosomes are also a promising class of novel drug delivery vehicles owing to their ability to shield their payload from chemical and enzymatic degradations as well as to evade recognition by and subsequent removal by the immune system. Combined with a new class of affinity ligands known as aptamers or chemical antibodies, molecularly targeted exosomes are poised to become the next generation of smartly engineered nanovesicles for precision medicine. Here, recent advances in targeted exosomal delivery systems engineered by aptamer for future strategies to promote human health using this class of human-derived nanovesicles are summarized.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.

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“…The ability of blood to clot is an essential biological response that helps to maintain haemostasis and prevents excessive blood loss after tissue/vessel injury [11][12][13][14]. The clotting cascade in mammals is well understood, and the crucial step is the activation of prothrombin by a prothrombinase complex.…”

Section: Introductionmentioning

confidence: 99%

Next-generation rapid serum tube technology using prothrombin activator coagulant: fast, high-quality serum from normal samples

Zhao

Dimeski

Jersey

et al. 2018

Clinical Chemistry and Laboratory Medicine (CCLM)

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BackgroundIncomplete blood clotting or latent clotting in serum is a common laboratory problem, especially for patients on anticoagulant therapy or when serum tubes are centrifuged before clotting is completed. We describe a novel approach to producing high-quality serum using snake venom prothrombin activator complex (OsPA) as an additive in blood collection tubes for non-anticoagulated (normal) individuals.MethodsPlasma clotting assays were performed using a Hyland-Clotek instrument. Blood clotting was visually observed, and thromboelastography was also performed to determine the important parameters of coagulation. Thrombin generation was assayed using the chromogenic substrate S-2238, and biochemical analytes in the serum were determined on chemistry and immunoassay analysers. Fibrinogen was determined by either ELISA or Clauss fibrinogen assay.ResultsWe initially showed that OsPA had strong coagulation activity in clotting not only recalcified citrated plasma and recalcified citrated whole blood, but also fresh whole blood in a clinical setting. The use of TEG clearly showed improved speed of clotting and generation of a firmer clot. We also showed that the use of OsPA to produce serum did not interfere with the determination of commonly measured biochemical analytes. The underlying clotting mechanism involves a burst of thrombin production at the initial stages of the clotting process upon contact with prothrombin in blood.ConclusionsThese results demonstrate rapid generation of high-quality serum, contributing to faster turnaround times with standardised quality samples, for accurate analyte determinations in normal individuals.

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Probing the Coagulation Pathway with Aptamers Identifies Combinations that Synergistically Inhibit Blood Clot Formation

Cited by 16 publications

References 38 publications

Aptamers as targeted therapeutics: current potential and challenges

Aptamers as targeted therapeutics: current potential and challenges

Exosomes and Nanoengineering: A Match Made for Precision Therapeutics

Next-generation rapid serum tube technology using prothrombin activator coagulant: fast, high-quality serum from normal samples

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