Highly Selective Aptamer‐Molecularly Imprinted Polymer Hybrids for Recognition of SARS‐CoV‐2 Spike Protein Variants

Mark V. Sullivan; Francia Allabush; Harriet Flynn; Banushan Balansethupathy; Joseph A. Reed; Edward T. Barnes; Callum Robson; Phoebe O'Hara; Laura J. Milburn; David Bunka; Arron Tolley; Paula M. Mendes; James H. R. Tucker; Nicholas W. Turner

doi:10.1002/gch2.202200215

Highly Selective Aptamer‐Molecularly Imprinted Polymer Hybrids for Recognition of SARS‐CoV‐2 Spike Protein Variants

Mark V. Sullivan, Francia Allabush, Harriet Flynn, Banushan Balansethupathy, Joseph A. Reed, Edward T. Barnes, Callum Robson, Phoebe O'Hara, Laura J. Milburn, David Bunka, Arron Tolley, Paula M. Mendes, James H. R. Tucker, Nicholas W. Turner^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Virus recognition has been driven to the forefront of molecular recognition research due to the COVID‐19 pandemic. Development of highly sensitive recognition elements, both natural and synthetic is critical to facing such a global issue. However, as viruses mutate, it is possible for their recognition to wane through changes in the target substrate, which can lead to detection avoidance and increased false negatives. Likewise, the ability to detect specific variants is of great interest for clinical analysis of all viruses. Here, a hybrid aptamer‐molecularly imprinted polymer (aptaMIP), that maintains selective recognition for the spike protein template across various mutations, while improving performance over individual aptamer or MIP components (which themselves demonstrate excellent performance). The aptaMIP exhibits an equilibrium dissociation constant of 1.61 nM toward its template which matches or exceeds published examples of imprinting of the spike protein. The work here demonstrates that “fixing” the aptamer within a polymeric scaffold increases its capability to selectivity recognize its original target and points toward a methodology that will allow variant selective molecular recognition with exceptional affinity.

Original language	English
Article number	2200215
Number of pages	11
Journal	Global Challenges
Volume	7
Issue number	6
Early online date	20 Mar 2023
DOIs	https://doi.org/10.1002/gch2.202200215
Publication status	Published - Jun 2023

Bibliographical note

Acknowledgments:
N.W.T. and M.V.S. would like to thank EPSRC for financial support for this work (EP/S003339/1 and EP/V046594/1). F.A., J.H.R.T., and P.M.M. would like to acknowledge the EPSRC (EP/K027263/1) and the ERC (Consolidator Grant 614787) for financial support as well as the Centre for Chemical and Materials Analysis in the School of Chemistry, University of Birmingham, for technical support.

Keywords

aptamers
molecular imprinting
nanoparticles
SARS-CoV-2
viral detection
viral variants

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10.1002/gch2.202200215Licence: Creative Commons: Attribution (CC BY)

SullivanM2023HighlyFinal published version, 2 MBLicence: Creative Commons: Attribution (CC BY)

FP7_ERC - GLYCOSURF
Mendes, P. (Principal Investigator)
European Commission, European Commission - Management Costs
1/12/14 → 31/05/21
Project: Research
Surface-Based Molecular Imprinting for Glycoprotein Recognition
Fossey, J. (Co-Investigator) & Mendes, P. (Principal Investigator)
Engineering & Physical Science Research Council
30/09/13 → 31/05/19
Project: Research Councils

Cite this

Sullivan, M. V., Allabush, F., Flynn, H., Balansethupathy, B., Reed, J. A., Barnes, E. T., Robson, C., O'Hara, P., Milburn, L. J., Bunka, D., Tolley, A., Mendes, P. M., Tucker, J. H. R., & Turner, N. W. (2023). Highly Selective Aptamer‐Molecularly Imprinted Polymer Hybrids for Recognition of SARS‐CoV‐2 Spike Protein Variants. Global Challenges, 7(6), Article 2200215. https://doi.org/10.1002/gch2.202200215

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title = "Highly Selective Aptamer‐Molecularly Imprinted Polymer Hybrids for Recognition of SARS‐CoV‐2 Spike Protein Variants",

abstract = "Virus recognition has been driven to the forefront of molecular recognition research due to the COVID‐19 pandemic. Development of highly sensitive recognition elements, both natural and synthetic is critical to facing such a global issue. However, as viruses mutate, it is possible for their recognition to wane through changes in the target substrate, which can lead to detection avoidance and increased false negatives. Likewise, the ability to detect specific variants is of great interest for clinical analysis of all viruses. Here, a hybrid aptamer‐molecularly imprinted polymer (aptaMIP), that maintains selective recognition for the spike protein template across various mutations, while improving performance over individual aptamer or MIP components (which themselves demonstrate excellent performance). The aptaMIP exhibits an equilibrium dissociation constant of 1.61 nM toward its template which matches or exceeds published examples of imprinting of the spike protein. The work here demonstrates that “fixing” the aptamer within a polymeric scaffold increases its capability to selectivity recognize its original target and points toward a methodology that will allow variant selective molecular recognition with exceptional affinity.",

keywords = "aptamers, molecular imprinting, nanoparticles, SARS-CoV-2, viral detection, viral variants",

author = "Sullivan, {Mark V.} and Francia Allabush and Harriet Flynn and Banushan Balansethupathy and Reed, {Joseph A.} and Barnes, {Edward T.} and Callum Robson and Phoebe O'Hara and Milburn, {Laura J.} and David Bunka and Arron Tolley and Mendes, {Paula M.} and Tucker, {James H. R.} and Turner, {Nicholas W.}",

note = "Acknowledgments: N.W.T. and M.V.S. would like to thank EPSRC for financial support for this work (EP/S003339/1 and EP/V046594/1). F.A., J.H.R.T., and P.M.M. would like to acknowledge the EPSRC (EP/K027263/1) and the ERC (Consolidator Grant 614787) for financial support as well as the Centre for Chemical and Materials Analysis in the School of Chemistry, University of Birmingham, for technical support.",

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Sullivan, MV, Allabush, F, Flynn, H, Balansethupathy, B, Reed, JA, Barnes, ET, Robson, C, O'Hara, P, Milburn, LJ, Bunka, D, Tolley, A, Mendes, PM , Tucker, JHR & Turner, NW 2023, 'Highly Selective Aptamer‐Molecularly Imprinted Polymer Hybrids for Recognition of SARS‐CoV‐2 Spike Protein Variants', Global Challenges, vol. 7, no. 6, 2200215. https://doi.org/10.1002/gch2.202200215

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AU - Flynn, Harriet

AU - Balansethupathy, Banushan

AU - Reed, Joseph A.

AU - Barnes, Edward T.

AU - Robson, Callum

AU - O'Hara, Phoebe

AU - Milburn, Laura J.

AU - Bunka, David

AU - Tolley, Arron

AU - Mendes, Paula M.

AU - Tucker, James H. R.

AU - Turner, Nicholas W.

N1 - Acknowledgments: N.W.T. and M.V.S. would like to thank EPSRC for financial support for this work (EP/S003339/1 and EP/V046594/1). F.A., J.H.R.T., and P.M.M. would like to acknowledge the EPSRC (EP/K027263/1) and the ERC (Consolidator Grant 614787) for financial support as well as the Centre for Chemical and Materials Analysis in the School of Chemistry, University of Birmingham, for technical support.

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Y1 - 2023/6

N2 - Virus recognition has been driven to the forefront of molecular recognition research due to the COVID‐19 pandemic. Development of highly sensitive recognition elements, both natural and synthetic is critical to facing such a global issue. However, as viruses mutate, it is possible for their recognition to wane through changes in the target substrate, which can lead to detection avoidance and increased false negatives. Likewise, the ability to detect specific variants is of great interest for clinical analysis of all viruses. Here, a hybrid aptamer‐molecularly imprinted polymer (aptaMIP), that maintains selective recognition for the spike protein template across various mutations, while improving performance over individual aptamer or MIP components (which themselves demonstrate excellent performance). The aptaMIP exhibits an equilibrium dissociation constant of 1.61 nM toward its template which matches or exceeds published examples of imprinting of the spike protein. The work here demonstrates that “fixing” the aptamer within a polymeric scaffold increases its capability to selectivity recognize its original target and points toward a methodology that will allow variant selective molecular recognition with exceptional affinity.

AB - Virus recognition has been driven to the forefront of molecular recognition research due to the COVID‐19 pandemic. Development of highly sensitive recognition elements, both natural and synthetic is critical to facing such a global issue. However, as viruses mutate, it is possible for their recognition to wane through changes in the target substrate, which can lead to detection avoidance and increased false negatives. Likewise, the ability to detect specific variants is of great interest for clinical analysis of all viruses. Here, a hybrid aptamer‐molecularly imprinted polymer (aptaMIP), that maintains selective recognition for the spike protein template across various mutations, while improving performance over individual aptamer or MIP components (which themselves demonstrate excellent performance). The aptaMIP exhibits an equilibrium dissociation constant of 1.61 nM toward its template which matches or exceeds published examples of imprinting of the spike protein. The work here demonstrates that “fixing” the aptamer within a polymeric scaffold increases its capability to selectivity recognize its original target and points toward a methodology that will allow variant selective molecular recognition with exceptional affinity.

KW - aptamers

KW - molecular imprinting

KW - nanoparticles

KW - SARS-CoV-2

KW - viral detection

KW - viral variants

U2 - 10.1002/gch2.202200215

DO - 10.1002/gch2.202200215

M3 - Article

SN - 2056-6646

VL - 7

JO - Global Challenges

JF - Global Challenges

IS - 6

M1 - 2200215

ER -

Highly Selective Aptamer‐Molecularly Imprinted Polymer Hybrids for Recognition of SARS‐CoV‐2 Spike Protein Variants

Abstract

Bibliographical note

Keywords

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Projects

FP7_ERC - GLYCOSURF

Surface-Based Molecular Imprinting for Glycoprotein Recognition

Cite this