From Selection to Use: Aptamers as Targeting Reagents in Hematology.

Aptamers are synthetic nucleic acid ligands that have been proposed as alternatives to antibodies for targeting molecules and cells. In hematology, most reviews have organized aptamer literature around diseases or technological platforms. This framing has obscured how unevenly different blood cell types have been covered. In this review, we present developed aptamers organized by blood cell lineages. Specifically, we examine aptamers for B cells, T cells, natural killer cells, and red blood cells. This organization revealed a strong concentration on a small set of canonical surface markers and on malignant cell models. A parallel gap appeared in aptamers that distinguish differentiation stages or functional cell states. Within this framework, we evaluated reported applications, design strategies, and experimental use cases alongside persistent limitations in target selection and biological resolution. Our analysis highlighted both practical constraints and conceptual blind spots in current blood-cell-targeting aptamer research. Together, these observations defined a set of clear opportunities for expanding aptamer development toward more state-resolved, biologically informative, and clinically relevant targeting strategies.