Approved treatment — aptamer drugs: U.S. FDA pegaptanib (2004) and avacincaptad pegol (2023); Japan avacincaptad pegol (conditional approval, 2025) — all for eye diseases Aptamers for cancer: in clinical trials (e.g., German GLORIA phase 1/2) Sources: Theranostics 2022 and Pharmaceutics 2025 reviews, Nature Communications 2024, approval reports
The difference between an aptamer and an antibody comes down to this: the same "key" made from different materials. Both are targeted drugs that bind precisely to a specific protein in the body, but an antibody is a large protein made by living cells (about 150–170 kDa), while an aptamer is a small, chemically synthesized nucleic acid (about 12–30 kDa). Aptamer drugs are already approved for eye diseases in the U.S. (2004 and 2023) and Japan (2025) and are used in patient care, and results from human trials in cancer continue to build.
What do aptamers and antibodies have in common?
Every protein in the body has its own shape. Antibodies and aptamers are both "molecular keys" that fit the shape of a target protein, blocking its action or marking where it is. That is why both are developed as targeted therapies and also used as markers in diagnostic tests and imaging.
Antibodies are Y-shaped proteins that the immune system naturally makes against bacteria and viruses, and many of today's cancer drugs are antibody medicines built on this principle. An aptamer binds its target through the 3-D structure formed when a short single strand of DNA or RNA folds on itself. Working through its "shape" rather than by carrying genetic information is what sets aptamers apart from other nucleic acid medicines. Where aptamers sit within nucleic acid medicine is covered in Nucleic acid medicine and aptamers: start by separating the terms.
Aptamer vs antibody at a glance
| Feature | Aptamer | Antibody |
|---|---|---|
| Material | Short single-stranded DNA or RNA (nucleic acid) | Protein (amino acids) |
| Size (molecular weight) | About 12–30 kDa | About 150–170 kDa |
| Discovery and production | Found by test-tube selection (SELEX), then chemically synthesized | Produced by culturing living cells |
| Batch-to-batch variation | Low | Careful control of cell culture is important |
| Immune response | Reported as low or minimal | Depending on the drug, the body can make antibodies against it |
| Heat and pH stability | Less sensitive; refolds and regains function after heat unfolding | A protein, so temperature control matters |
| Time in the body | Small, so quickly cleared by the kidneys → extended with PEG and other changes | Stays in the blood relatively long |
| Reversing the effect | Can be stopped with a matching nucleic acid (antidote) | Generally no dedicated antidote |
Sources: Bohrmann L et al., Theranostics 2022 / Bege M et al., Pharmaceutics 2025. Molecular weight (kDa, kilodaltons) varies by drug.
Strengths of aptamers
- Small size: at about one-fifth the size of an antibody or less, aptamers move easily through tissue, and in experimental models they penetrate deep into tumor masses and stay there.
- Chemical synthesis: no cells need to be grown, so production is more economical and reproducible, with little quality difference between batches.
- Storage stability: less sensitive to pH and temperature changes, giving a longer shelf life; even if heat unfolds them, they refold on cooling and regain their function.
- Low immune response: because they are not proteins, the immune system rarely treats them as foreign and attacks them.
- Reversible action: adding a nucleic acid that pairs with the aptamer pulls it off its target. This means an "antidote" can be designed to switch the drug off when needed, which is rare among antibody drugs.
How are aptamer weaknesses overcome?
An unmodified aptamer is easily cut by nucleic-acid-degrading enzymes in the blood, and because it is smaller than 5 nm across it is filtered quickly by the kidneys, giving a plasma half-life measured in minutes. Aptamers used as drugs are therefore chemically improved in several ways.
- Sugar modifications (2′-fluoro, 2′-O-methyl): help resist enzymes and bind the target more tightly. They were used in pegaptanib, the first aptamer drug.
- PEG (polyethylene glycol) attachment: makes the molecule larger to slow kidney clearance. Pegaptanib carries two 20 kDa PEG chains, and "pegol" in a drug name signals an attached PEG.
- Mirror-image nucleic acids (L-RNA, Spiegelmers): built in a mirror-image form that natural enzymes do not recognize. Olaptesed pegol, now in cancer trials, uses this approach.
- End caps (inverted dT cap): protect against trimming from the end of the strand.
These technologies made it possible for aptamers to be approved as real medicines. The route of administration matters too: both approved drugs are injected directly into the eye (vitreous) so they stay where they are needed.
Aptamer drugs approved for patients
| Drug | Target | Approval | Condition and pivotal trials |
|---|---|---|---|
| Pegaptanib (Macugen) | VEGF (blood-vessel growth factor) | U.S. FDA December 2004; Europe January 2006 | Neovascular age-related macular degeneration. In phase 3 (V.I.S.I.O.N., 1,186 patients), 70% (0.3 mg) lost fewer than 15 letters at week 54 versus 55% with sham injection |
| Avacincaptad pegol (Izervay) | Complement protein C5 | U.S. FDA August 4, 2023; Japan September 2025 (conditional approval) | Geographic atrophy (an advanced form of dry macular degeneration). In phase 3 GATHER1 (448 patients) and GATHER2 (286 patients), lesion growth slowed by 27.7% and 14.3% at 12 months |
Sources: Bege M et al., Pharmaceutics 2025 / Foundation Fighting Blindness 2023 / Pharmaceutical Technology 2025. In Japan, avacincaptad pegol was described as the first treatment approved for geographic atrophy.
Pegaptanib was the world's first aptamer drug and the first VEGF-blocking drug, opening the way for later treatments aimed at the same target. Avacincaptad pegol, approved about 20 years later as the second aptamer drug, is also available to patients in Japan on the condition that post-marketing confirmatory studies continue.
How far have aptamers come in cancer?
In cancer, aptamers are at the stage where results from human clinical trials are building up. A leading example is olaptesed pegol (NOX-A12), developed by Germany's TME Pharma. In the phase 1/2 GLORIA trial in newly diagnosed glioblastoma with tumor remaining after surgery, weekly intravenous doses given with radiotherapy led to an imaging tumor response in 9 of 10 patients. Details, including the expansion cohort with bevacizumab, are in Aptamer cancer drug trial results.
Because aptamers are small and easy to link chemically to other molecules, they are also being actively studied as imaging markers that find cancer and as carriers that deliver anticancer drugs to cancer cells. Just as antibody-drug conjugates, which attach a cancer drug to an antibody, are already in use, aptamers are being developed in the same direction.
What to check when a Japanese clinic offers "aptamer therapy"
Some clinics in Japan offer "aptamer therapy" as self-pay care. These may be different products from the approved drugs above, so the following points help you compare accurately.
- What is the name of the aptamer used, and what protein does it target?
- Is the product an approved drug in any country, or is it in clinical trials?
- Have results in people been published in a medical journal?
- Can it be given alongside your current chemotherapy, immunotherapy or radiotherapy?
You can also see the scope of nucleic acid and aptamer information offered in Japan in our Nucleic Acid Medicine & Aptamers guide.
Questions for your doctor
- Is there a protein in my cancer that could be targeted? Is there an approved antibody drug or an aptamer in trials for that target?
- Between antibody drugs and aptamers, which has more evidence for my situation?
- Are there aptamer clinical trials I could join in Japan or elsewhere?
- If a new treatment is added, how would my current treatment schedule be adjusted?
Frequently asked questions
Which is better, an aptamer or an antibody?
They serve different purposes rather than one being better. Antibodies stay in the blood longer and many cancer drugs are already approved, while aptamers are small, chemically synthesized, cause little immune response and can be reversed. The actual choice is made by your care team based on the disease and approval status.
Are there approved aptamer drugs?
Yes. Pegaptanib (U.S., 2004) and avacincaptad pegol (U.S., 2023; Japan conditional approval, 2025) are approved and used for eye diseases. Aptamers for cancer continue to be developed in clinical trials.
Are "aptamer" and "aptamer therapy" the same as nucleic acid medicine?
Aptamers are one type of nucleic acid medicine. Other types, such as siRNA and antisense drugs, work by acting on genetic information, while aptamers work by binding to a target with their shape.
How are aptamer drugs given?
The two approved drugs are injected directly into the eye (vitreous). In the cancer trial, olaptesed pegol was given as a weekly intravenous infusion during radiotherapy. The method depends on the drug and the disease.
Related: Aptamer cancer drug trial results: olaptesed pegol phase 1/2 · What is oncolytic virus therapy? · CAR-NK vs CAR-T · Nucleic Acid Medicine & Aptamers guide
Sources
- Bohrmann L, Burghardt T, Haynes C, Saatchi K, Häfeli UO et al. Aptamers used for molecular imaging and theranostics – recent developments. Theranostics 2022;12(9):4010–4050
doi.org/10.7150/thno.72949
Checked: 2026-10-22 - Bege M, Ghanem Kattoub R, Borbás A. The 20th Anniversary of Pegaptanib (Macugen), the First Approved Aptamer Medicine: History, Recent Advances and Future Prospects of Aptamers in Therapy. Pharmaceutics 2025;17(3):394
doi.org/10.3390/pharmaceutics17030394
Checked: 2026-10-22 - Foundation Fighting Blindness — FDA Approves IZERVAY (avacincaptad pegol) for Geographic Atrophy (2023-08-05)
fightingblindness.org
Checked: 2026-10-22 - Pharmaceutical Technology — Astellas' Izervay gains conditional approval in Japan for GA treatment (2025-09)
pharmaceutical-technology.com
Checked: 2026-10-22 - Giordano FA, Layer JP, Leonardelli S et al. L-RNA aptamer-based CXCL12 inhibition combined with radiotherapy in newly-diagnosed glioblastoma: dose escalation of the phase I/II GLORIA trial. Nature Communications 2024;15
doi.org/10.1038/s41467-024-48416-9
Checked: 2026-10-22
Written by the FTH editorial team. Sources checked 2026-10-22 · Medical review: not applicable
This article is general information based on public sources and does not replace diagnosis or treatment. Please discuss treatment decisions with your medical team.
