Monoclonal antibodies play a vital role in research, diagnostics, and therapeutics. Many advancements have been made to improve the performance of monoclonal antibodies, specifically in the therapeutic area. Though antibodies are an ideal choice for many applications, there are some instances where an aptamer may be a better alternative. Some of the key differences between antibodies and aptamers are highlighted below and outlined in the Aptamers vs. Antibodies table. Learn more about aptamer advantages.
Selectivity: Aptamers are easily selected against small, non-immunogenic molecules and molecules that are toxic to antibody-producing cells
Size: Aptamers are about ten times smaller than antibodies, giving them better access to tissues and cells.
Synthesis: Chemical synthesis reduces lot-to-lot variability and eliminates many regulatory requirements associated with bioproduction
Aptamers vs. Antibodies Table
|Monoclonal Antibody||Aptamer||Aptamer Advantage|
|Development Time* (Delivery of 1st production batch)||~4 – 6 months||~1 – 3 months||Faster development time means faster time to market or publication|
|Development Process||Initial antibody generation requires an immune response in an animal model||Enrichment of an oligonucleotide library through SELEX process||Aptamers can be selected against toxic compounds and non-immunogenic compounds (3)|
|Size||~150 – 170 kDa (IgG)||~12 – 30 kDa (~30-80 nucleotides)||Due to their small size, aptamers can infiltrate tissues and sometimes cells. They also have a higher tendency to be non-toxic and non-immunogenic (1,2,3)|
|Optimal Working Concentration||Varies widely by application||~ 5 to 10 times lower than optimal antibody concentration for some applications||Due to lower molecular weight, there are typically five to ten times more aptamers than antibodies in a solution of the same concentration|
|Minimum Target Size||≥ 600 Daltons||≥ 60 Daltons||Target small molecules|
|Manufacturing Process||In vivo production; Cell culture||Chemical synthesis||Improved batch-to-batch consistency, animal/cell-free process, simple scale-up and purification; Aptamers can be selected under non-physiological conditions; Less costly to manufacture GMP-grade aptamers in large quantities|
|Modification||Antibodies are typically conjugated with one type of signaling or binding molecule||Aptamers can be modified at both the 5’ and 3’ end||Aptamers can be easily modified for attachment and signaling, often during aptamer synthesis|
|Stability||Antibodies are susceptible to high temperatures and pH changes; Denatured antibodies cannot be repaired||Aptamers are fairly stable at ambient temperature and are easily refolded if denatured||Aptamers have a longer shelf life and can be transported at ambient temperature (4)|
|Long-term Availability||Frozen cell stocks must be maintained for monoclonal antibody production||Specific nucleotide sequence (data) is stored for aptamer production||Aptamer sequences are easy to store and transfer to production sites. Sequences are not lost if a freezer goes down.|
*Actual time will vary from one project to another
- Cao Z, Tong R, Mishra A, Xu W, Wong GCL, Cheng J, Lu Y: Reversible Cell-Specific Drug Delivery with Aptamer-Functionalized Liposomes. Angew. Chem. Int. Ed. 2009, 48:6494-6498.
- Ferreira CSM, Cheung MC, Missailidis S, Bisland S, Gariepy J: Phototoxic aptamers selectively enter and kill epithelial cancer cells. Nucl. Acids Res. 2009, 37:866-876.
- Jayasena, S. D. Aptamers: An emerging class of molecules that rival antibodies in diagnostics. Clinical Chemistry. 1999. 45(9):1628-50.
- Sun, H. et al. Oligonucleotide Aptamers: New Tools for Targeted Cancer Therapy. Molecular Therapy – Nucleic Acids. 2014. 3, e182. Doi: 10.1038/mtna.2014.32.