Author:
Percze Krisztina,Tolnai Zoltán János,Eleveld Marc,Ou Li,Du Haijuan,Olia Adam S.,Kwong Peter D.,de Jonge Marien I.,Mészáros Tamás
Abstract
AbstractRespiratory syncytial virus (RSV) is a leading cause of serious and even fatal acute lower respiratory tract infections in infants and in the elderly. Potent RSV neutralization has been achieved by antibodies that selectively bind the prefusion form of the viral fusion (F) protein. We hypothesised that similar potent neutralization could be achieved using F protein targeting aptamers. Aptamers have yet to reach their translational potential for therapeutics or diagnostics due to their short half-life and limited range of target-aptamer interactions; these shortcomings can, however, be ameliorated by application of amino acid-like side chain holding nucleotides. In this study, a stabilized version of the prefusion RSV F protein was targeted by aptamer selection using an oligonucleotide library holding a tryptophan-like side chain. This process resulted in aptamers that bound the F protein with high affinity and differentiated between its pre- and postfusion conformation. Identified aptamers inhibited viral infection of lung epithelial cells. Moreover, introduction of modified nucleotides extended aptamer half-lives. Our results suggest that targeting aptamers to the surface of viruses could yield effective drug candidates, which could keep pace with the continuously evolving pathogens.
Funder
Hungarian National Research, Development and Innovation Office
Ministry of Innovation and Technology of Hungary
Intramural Research Program of the Vaccine Research Center
Semmelweis University
Publisher
Springer Science and Business Media LLC
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