High Mannose-Specific Aptamers for Broad-Spectrum Virus Inhibition and Cancer Targeting

High mannose oligosaccharides are characteristic and essential for immune evasion of many viruses and cancer cells.They are potential targets for viral inhibition and cancer diagnosis/therapy.Particularly,high mannose-binding reagents may be a unique asset for fighting the ongoing and mutating SARSCoV-2 virus.Lectins are prevailing reagents for saccharide binding but suffer from inadequate specificity and apparent immunogenicity.Meanwhile,other reagents for the same purpose,such as antibodies and aptamers,have rarely been reported.Herein,using molecularly imprinted magnetic nanoparticles as a potent platform,we report a smart selection method for fine screening of high mannose-specific aptamers.Monovalent aptamers were first effectively screened within eight rounds of selection.Multivalent aptamers,in the forms of dendritic polymer or tetrahedral DNA nanostructure(TDN),were further engineered.The aptamers exhibited high affinity toward the spike protein of SARS-CoV-2 and the envelope protein GP120 of HIV.Both the monovalent aptamer and its TDN form exhibited a certain inhibition effect to the SARS-CoV-2 pseudovirus.On the other hand,both the monovalent aptamer and its dendritic form permitted the recognition of cancer cells over normal cells.Therefore,as unprecedented reagents for broad-spectrum viral inhibition and cancer targeting,these aptamers hold great promise for clinical treatment and diagnosis.