RAID3 - An interleukin-6 receptor-binding aptamer with post-selective modification-resistant affinity

Mittelberger, Florian; Meyer, Cindy; Waetzig, Georg H.; Zacharias, Martin; Valentini, Erica; Svergun, Dmitri I.; Berg, Katharina; Lorenzen, Inken; Grötzinger, Joachim; Rose-John, Stefan; Hahn, Ulrich

doi:10.1080/15476286.2015.1079681

Cited by 24 publications

(22 citation statements)

References 52 publications

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“…41 Against this background, one considerable aspect for future analyses is the investigation of hIL-6R affinity toward other Gquadruplexes as, next to AIR-3(A), 2 other aptamers (AID-1 and RAID3) independently selected for hIL-6R, were shown to form GQs. 35,42 Additionally, AID-1 also showed affinity for gp120 as well as HIV-1 integrase which in turn is known to bind GQs. 43 The number of identified GQ binding proteins constantly increases, 17 especially as during the past years the regulatory potential of GQs in biological processes moved into focus of research.…”

Section: Discussionmentioning

confidence: 99%

“…29 Next to former studies dealing with stabilization by 2 0 -F-pyrimidines this presented another possibility to post-selectively modify hIL-6R specific aptamers with retained affinity. 31,35 In order to further investigate the tolerance to nucleotide modifications, we identified different aptamer variants containing nucleoside analogs gemcitabine (2 0 ,2 0 -Difluorodeoxycytidine) and 5-FdU which maintained binding capacity to hIL-6R and investigated their stability.…”

Section: Affinity Of Air-3 Variants For Hil-6rmentioning

confidence: 99%

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Structure and target interaction of a G-quadruplex RNA-aptamer

et al. 2016

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G-quadruplexes have recently moved into focus of research in nucleic acids, thereby evolving in scientific significance from exceptional secondary structure motifs to complex modulators of gene regulation. Aptamers (nucleic acid based ligands with recognition properties for a specific target) that form Gquadruplexes may have particular potential for therapeutic applications as they combine the characteristics of specific targeting and Gquadruplex mediated stability and regulation. We have investigated the structure and target interaction properties of one such aptamer: AIR-3 and its truncated form AIR-3A. These RNA aptamers are specific for human interleukin-6 receptor (hIL-6R), a key player in inflammatory diseases and cancer, and have recently been exploited for in vitro drug delivery studies. With the aim to resolve the RNA structure, global shape, RNA: protein interaction site and binding stoichiometry, we now investigated AIR-3 and AIR-3A by different methods including RNA structure probing, Small Angle X-ray scattering and microscale thermophoresis. Our findings suggest a broader spectrum of folding species than assumed so far and remarkable tolerance toward different modifications. Mass spectrometry based binding site analysis, supported by molecular modeling and docking studies propose a general Gquadruplex affinity for the target molecule hIL-6R.

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Section: Discussionmentioning

confidence: 99%

Section: Affinity Of Air-3 Variants For Hil-6rmentioning

confidence: 99%

Structure and target interaction of a G-quadruplex RNA-aptamer

et al. 2016

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“…These three studies clearly show how aptamer-induced CD molecule internalization can be effectively used for targeted drug delivery. Recently, Ulrich’s team conducted other studies to expand the usage of their developed aptamer for CD126 to in vivo studies and clinical trials by modifying the aptamer to become more resistant to nucleases 104, 105…”

Section: Main Textmentioning

confidence: 99%

Aptamers for CD Antigens: From Cell Profiling to Activity Modulation

Nozari

Berezovski

2017

Molecular Therapy - Nucleic Acids

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Nucleic acid-based aptamers are considered to be a promising alternative to antibodies because of their strong and specific binding to diverse targets, fast and inexpensive chemical synthesis, and easy labeling with a fluorescent dye or therapeutic agent. Cluster of differentiation (CD) proteins are among the most popular antigens for aptamers on the cell surface. These anti-CD aptamers could be used in cell biology and biomedicine, from simple cell phenotyping by flow cytometry or fluorescent microscopy to diagnosis and treatment of HIV/AIDS to cancer and immune therapies. The unique feature of aptamers is that they can act simultaneously as an agonist and antagonist of CD receptors depending on a degree of aptamer oligomerization. Aptamers can also deliver small interfering RNA to silence vital genes in CD-positive cells. In this review, we summarize nucleic acid sequences of anti-CD aptamers and their use, which have been validated in multiple studies.

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“…QDs are applied in both, in vitro analysis and in vivo 152 imaging, due to their excellent optical properties. However, they are toxic compounds and 153 several strategies have been developed to make them biocompatible and non-toxic [51]. 154 Nanorods are rod shape metal nanoparticles that generate heat when excited with IR light.…”

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confidence: 99%