Nucleic acid aptamers are short, single-stranded DNA or RNA molecules that fold into specific three-dimensional structures, enabling them to bind to target molecules with high affinity and specificity. The word “aptamer” comes from the Latin aptus (to fit) and the Greek meros (part).
Size: Typically 20-80 nucleotides in length
Binding affinity: Often in nanomolar to picomolar range
Specificity: Can distinguish between closely related molecules
Synthetic origin: Created through in vitro selection processes
Aptamers are developed through SELEX (Systematic Evolution of Ligands by EXponential enrichment), an iterative process involving:
Incubation of a random nucleic acid library with the target
Separation of binding sequences from non-binders
Amplification of selected sequences
Repetition over multiple rounds (typically 8-15 cycles)
Compared to antibodies, aptamers offer:
Chemical synthesis: Reproducible production without batch variability
Modifiability: Can be chemically modified for stability and functionality
Temperature stability: Can often be refolded after denaturation
Non-immunogenic: Low immunogenicity in therapeutic applications
Target range: Can bind to toxins, non-immunogenic molecules, and small compounds
Diagnostics: Biosensors, detection assays (aptasensors)
Therapeutics: Targeted drug delivery, direct inhibitors (“chemical antibodies”)
Research tools: Protein detection, cellular imaging, biomarker discovery
Analytical chemistry: Affinity purification, chromatography
Susceptibility to nuclease degradation (especially RNA aptamers)
Renal clearance due to small size
Limited cellular uptake without delivery systems
Need for optimization of chemical modifications
Pegaptanib (Macugen): First FDA-approved aptamer drug for age-related macular degeneration
AS1411: A G-quadruplex forming DNA aptamer in clinical trials for cancer
Research focuses on improved chemical modifications, delivery systems, and expanding the range of targetable molecules. Aptamers represent a versatile class of recognition elements bridging the molecular recognition properties of antibodies with the chemical advantages of nucleic acids.
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