Aptamers are a class of therapeutic molecules often called “chemical antibodies” because they perform the same function as traditional antibody drugs (binding to a target), but they are made from an entirely different material: short strands of nucleic acid (DNA or RNA) rather than complex proteins.
1. What Aptamers Are and How They Work
Aptamers rely on a simple but brilliant principle: shape.
Structure: An aptamer is a relatively small, synthetic molecule. When placed in the body, it folds itself into a precise, three-dimensional structure—like a lock or a molecular glove.
Binding: This specific folded shape allows the aptamer to bind to a target molecule (a protein, a virus, or an enzyme) with very high affinity and specificity.
Action: Once bound, the aptamer inhibits the target’s function, effectively turning off the disease-causing activity.
2. Key Advantages Over Traditional Antibodies
Aptamers offer several significant benefits that address the cost and stability issues associated with large protein-based antibodies:
| Feature | Aptamer Benefit | Antibody Drawback |
| Manufacturing | Low Cost: Synthesized chemically, ensuring high purity and stable, low-cost production. | High Cost: Must be produced in complex, expensive biological cell systems (like CHO cells). |
| Shelf Stability | Excellent Stability: Can be stored as a dry powder at room temperature, eliminating the need for refrigeration. | Poor Stability: Requires continuous cold chain storage (refrigeration). |
| Immune Response | Low Immunogenicity: As nucleic acids, they are generally not seen as foreign by the immune system, leading to fewer side effects. | Risk of Immunogenicity: Can sometimes trigger an immune response (ADA) against the drug itself. |
| Tissue Penetration | Small Size: Their small size (about 1/10th the size of an antibody) allows them to penetrate dense tissues, like solid tumors or the eye, more easily. | Large Size: Their size can restrict access to certain anatomical sites. |
3. The Discovery Engine: SELEX
Aptamers are discovered using an in vitro (in the test tube) process called SELEX (Systematic Evolution of Ligands by Exponential Enrichment).
Instead of relying on biological processes (like immunizing an animal), SELEX uses synthetic chemistry to find the perfect binding molecule:
A vast library of trillions of random nucleic acid sequences is created.
The library is mixed with the target molecule.
Only the sequences that bind are kept and amplified.
This cycle is repeated until a sequence with extremely high affinity and specificity is isolated.
4. Clinical Success and Regulatory Acceptance
The FDA has approved two distinct aptamer drugs, confirming their clinical viability and regulatory acceptance:
| Drug Name | Approval Year | Target | Indication |
| Macugen (Pegaptanib) | 2004 | VEGF165 (Blood Vessel Growth Factor) | Wet Age-related Macular Degeneration (AMD) |
| Avacincaptad Pegol (ZIMURGA) | 2023 | Complement Factor C5 (Part of the immune system) | Geographic Atrophy (GA), a form of dry AMD |
Both approved aptamers rely on a crucial chemical modification-pegylation. This process is essential because it shields the aptamer from being rapidly broken down by enzymes in the blood, ensuring the drug lasts long enough to be therapeutically effective.
Aptamers continue to be a focus area in drug development, particularly for targets where high stability, low cost, or excellent tissue penetration is mandatory.