In this study, we (three independent research groups) evaluated the binding characteristics of various published RNA and DNA aptamers targeting the spike protein of the SARS-CoV-2 virus. Employing different techniques we discovered discrepancies in the reported specificity and affinity among several of the published aptamers and want to underline the importance of standardized methods, the impact of biophysical techniques, and the controls used for aptamer characterization.
We have developed and engineered a serum-stable RNA aptamer specific for SARS-CoV-2 spike protein. We further show that scaffolding three aptamers together increases the binding efficiency to the low picomolar range and enables very efficient neutralization of SARS-CoV-2 infection in cells. The aptamer also shows high affinity for spike protein from variants of concern. Due to its small size and chemical stability, our aptamer holds potential as an alternative to antibodies and nanobodies targeting spike protein.
A Multi-Faceted Binding Assessment of Aptamers Targeting the SARS-CoV-2 Spike Protein
L. Civit, N. Moradzadeh, A. Jonczyk, P. Neckermann, B. Asbach, D. Peterhoff, R. Wagner, M. Famulok, G. Mayer*, J. Kjems, J. Valero*
IJMS 2024, 25, 4642
Recent Advances on Catenanes and Rotaxanes Made of DNA
Y. Ma, Z. Yu, J. Valero
Mechanically Interlocked Materials 2024, 195–216
Specific Detection of Proteins by a Nanobody-Functionalized Nanopore Sensor
X. Zhang, N. S. Galenkamp, N. J. van der Heide, J. Moreno, G. Maglia*, J. Kjems*
ACS Nano 2023, 17, 9167–9177
A Self-Regulating DNA Rotaxane Linear Actuator Driven by Chemical Energy
Z. Yu, M. Centola, J. Valero*, M. Matthies, P. Šulc, M. Famulok
J. Am. Chem. Soc. 2021, 143, 13292–13298
A serum-stable RNA aptamer specific for SARS-CoV-2 neutralizes viral entry
J. Valero*, L. Civit, D. M. Dupont, D. Selnihhin, L. S. Reinert, M. Idorn, B. A. Israels, A. M. Bednarz, C. Bus, B. Asbach, D. Peterhoff, F. S. Pedersen, V. Birkedal, R. Wagner, S. R. Paludan, J. Kjems*
Proc. Natl. Acad. Sci. U.S.A. 2021, 118
Mechanisms, Methods of Tracking and Applications of DNA Walkers: A Review
J. Valero*, M. Škugor
ChemPhysChem 2020, 21, 1971–1988
Regeneration of Burnt Bridges on a DNA Catenane Walker
J. Valero*, M. Famulok
Angew Chem Int Ed 2020, 59, 16366–16370
Design, assembly, characterization, and operation of double-stranded interlocked DNA nanostructures
J. Valero, M. Centola, Y. Ma, M. Škugor, Z. Yu, M. W. Haydell, D. Keppner, M. Famulok*
Nat Protoc 2019, 14, 2818–2855
Orthogonally Photocontrolled Non‐Autonomous DNA Walker
M. Škugor, J. Valero*, K. Murayama, M. Centola, H. Asanuma, M. Famulok*
Angew Chem Int Ed 2019, 58, 6948–6951
A bio-hybrid DNA rotor–stator nanoengine that moves along predefined tracks
J. Valero, N. Pal, S. Dhakal, N. G. Walter, M. Famulok*
Nature Nanotech 2018, 13, 496–503
Expanding the Toolbox of Photoswitches for DNA Nanotechnology Using Arylazopyrazoles
V. Adam, D. K. Prusty, M. Centola, M. Škugor, J. S. Hannam, J. Valero, B. Klöckner, M. Famulok*
Chemistry A European J 2018, 24, 1062–1066
Temporal and Reversible Control of a DNAzyme by Orthogonal Photoswitching
M. W. Haydell, M. Centola, V. Adam, J. Valero*, M. Famulok*
J. Am. Chem. Soc. 2018, 140, 16868–16872
Allosteric Control of Oxidative Catalysis by a DNA Rotaxane Nanostructure
M. Centola, J. Valero*, M. Famulok*
J. Am. Chem. Soc. 2017, 139, 16044–16047
Interlocked DNA topologies for nanotechnology
J. Valero, F. Lohmann, M. Famulok
Current Opinion in Biotechnology 2017, 48, 159–167
Single‐Stranded Tile Stoppers for Interlocked DNA Architectures
J. Valero, F. Lohmann, D. Keppner, M. Famulok
ChemBioChem 2016, 17, 1146–1149
Cellular Antisense Activity of PNA-Oligo(bicycloguanidinium) Conjugates Forming Self-Assembled Nanoaggregates
J. Valero, T. Shiraishi, J. de Mendoza, P. E. Nielsen
ChemBioChem 2015, 16, 1593–1600
Sequence-selective DNA binding with cell-permeable oligoguanidinium–peptide conjugates
J. Mosquera, M. I. Sánchez, J. Valero, J. de Mendoza, M. E. Vázquez, J. L. Mascareñas
Chem. Commun. 2015, 51, 4811–4814
A novel family of structurally stable double stranded DNA catenanes
F. Lohmann, J. Valero, M. Famulok
Chem. Commun. 2014, 50, 6091–6093
Enhancing molecular recognition in electron donor-acceptor hybrids via cooperativity
R. M. K. Calderon, J. Valero, B. Grimm, J. de Mendoza, D. M. Guldi
J. Am. Chem. Soc. 2014, 136, 11436–11443
Logic Gating by Macrocycle Displacement Using a Double‐Stranded DNA [3]Rotaxane Shuttle
F. Lohmann, J. Weigandt, J. Valero, M. Famulok*
Angew Chem Int Ed 2014, 53, 10372–10376
A tetraguanidinium macrocycle for the recognition and cavity expansion of calix[4]arene tetraoxoanions
J. Valero, J. de Mendoza
Supramolecular Chemistry 2013, 25, 728–740
Anion-responsive diguanidinium-based chiral organogelators
J. Valero, B. Escuder*, J. F. Miravet, J. de Mendoza
Chemistry A European J 2012, 18, 13038–13047
Guanidinium-Based Receptors for Oxoanions
M. P. Conley, J. Valero, J. de Mendoza
Supramolecular Chemistry 2012
Non-peptidic cell-penetrating agents: synthesis of oligomeric chiral bicyclic guanidinium vectors
J. Valero, M. Van Gool, R. Pérez-Fernández, P. Castreño, J. Sánchez-Quesada, P. Prados, J. de Mendoza*
Org. Biomol. Chem. 2012, 10, 5417
Binding to protein surfaces by supramolecular multivalent scaffolds
V. Martos, P. Castreño, J. Valero, J. de Mendoza
Current Opinion in Chemical Biology 2008, 12, 698–706