A cross species CD200R1 immune checkpoint agonist with potent anti-inflammatory properties

Functional aptamers displaying agonistic or antagonistic properties are showing great promise in terms of modulating immune responses. Our group has recently developed pegylated DNA aptamers that can either block inflammatory responses (CD200R1agonist) or restore tumor-directed immune responses (PD-1 antagonist) in vivo . Here, we report the derivation and design of a cross species mouse/human CD200R1 DNA aptamer agonist that blocks inflammatory responses in mouse models of skin graft rejection and asthma. This DNA aptamer was discovered by performing NGS and comparing the resulting aptamer motifs derived from independently screening mouse and human CD200R1 as targets. Importantly, this m/hCD200R1 agonistic aptamer does not suppress cytotoxic T-lymphocyte (CTL) induction in 5 day allo-mixed lymphocyte cultures (MLCs) derived from CD200R1 knockout mice, indicating that its mode of action is directly linked to CD200R1 activation. This study suggests that one can derive agonistic DNA aptamers that can be verified as immunomodulators in mouse models with outcomes translatable to the treatment of human conditions.