Increased anticoagulant activity of thrombin-binding DNA aptamers by nanoscale organization on DNA nanostructures

Abstract

Thrombin inhibition via DNA aptamers has recently become a possibility. In this study, thrombin-binding DNA aptamers were further optimized by nanoscale organization on DNA nanostructures. The authors have created a novel, functional DNA nanostructure, which is a multi-aptamer inhibitor with activity eightfold higher than that of free aptamer. Reversal of thrombin inhibition was also achieved by single-stranded DNA antidotes, enabling significant control over the coagulation pathway.

In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging

“…Many initial studies using aptamers as delivery systems have produced exciting results as well. 3,4,[10][11][12][13][17][18][19][20] However, to realize the full potential of aptamer-targeted delivery systems, it is necessary to test for aptamers that are specific for clinically relevant cancer markers and demonstrate the effectiveness of the systems in vivo. Enormous progress has been made in the field in a very short period of time.…”

“…[5][6][7] In comparison to Abs, aptamers possess several obvious advantages. They are generally considered nonimmunogenic and biocompatible, much more stable to heat, pH, and organic solvents, easier to prepare and scale up, and with smaller molecular weight (8)(9)(10)(11)(12)(13)(14)(15). 3,8 The ssDNA or ssRNA can fold into welldefined 3D-structures and bind to their target with high affinity (μM-pM range) and specificity.…”

“…3,4,[10][11][12][13] In 2004, FDA-approved Macugen (pegaptanib) as an antiangiogenic therapeutic agent for neovascular (wet) age-related macular degeneration. In addition, a variety of other aptamers, such as AS1411, are currently under clinical trials.…”

Polyvalent nucleic acid aptamers and modulation of their activity: a focus on the thrombin binding aptamer

“…Multiple TBAs were linked at precise positions on a DNA nanostructure controlling and optimizing spacing and orientation of the aptamers in order to maximize the anticoagulant activity (Rangnekar et al, 2011). In particular, the high anticoagulant activity of TBA 15 was combined with the high binding affinity of TBA 29 by positioning them on a DNA weave-tiles at two of the four possible locations.…”

Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis

“…[28][29][30] Various technologies and different models have been developed for preparing nanomaterials, determining their properties, and promoting the development of nanomedicine. [31][32][33][34] Although nanodrugs have mainly focused on drug delivery systems, including liposomes, in the past decades, 35,36 recently, the selfassembly of single small molecules at nanoscale, 37,38 and their effects on biological activity, have been under intense investigation. 39,40 Besides, a series of self-assembled single small molecules, including β-carboline-3-carboxylic acid derivatives, are able to enhance the biological efficiency via their nanospecies.…”