Resources to consider reading before continuing:
Read about antibodies (Abs) as they occur naturally in the body & a note about Polyclonal Antibodies
Artist's rendering of antibodies binding to antigens on target cell
Artist's rendering of antibodies binding to antigens on target cell
Aptamers vs. Monoclonal Antibodies :
Read about Monoclonal Antibodies (mAbs)
- Stability: Proteins, the substance that make up mAbs, are notoriously known to be easily denatured. Denaturation is when a substance loses its structure, and thus its function, at certain temperatures. mAbs require refrigeration to avoid denaturation. Furthermore, proteins degrade over time - resulting in a limited shelf life.
Monoclonal Antibodies (mAbs)
Aptamers
Image Citation 16: RNA aptamer binding to a peptide
Image Citation 16: RNA aptamer binding to a peptide
vs.
- Stability: Aptamers can withstand repeated rounds of denaturation/renaturation, and retain their structures. They are also temperature resistant - enabling them to be stable at room temperature and do not require refrigeration. These properties result in an indefinite shelf life.
- Nuclease Degradation: Proteins, as amino acids, are not affected by nucleases.
- Nuclease Degradation: Aptamers, as nucleic acids, are subjected to nuclease degradation. Once introduced to the body, enzymes called nucleases break down nucleic acid bonds - destroying the aptamer. This limits half-life.
- In vitro capability: Although monoclonal antibodies can be selected in vitro, most mAbs must be produced in vivo. This means that the mAb production requires the use of a live animal to stimulate an immune response that produces the desired mAbs. Furthermore, this means that Abs are tied to
the environmental conditions of
the host animal - limiting adaptab-
ility.
- In vitro capability: Aptamers are produced in vitro through SELEX. This means that aptamer production does not require use of animals - negating possible animal abuses or deaths and the need to send animal protocols to the Institutional Animal Care and Use Committee. In vitro selection means aptamers can be manipulated to adapt to virtually any set of conditions.
- Immunogenicity: Antibodies are typically recognized by the body's immune system as foreign and dangerous, evoking an undesired immune response. This risk of an immune reaction increases with repeated dosing.
- Immunogenicity: Aptamers are not recognized by the body's immune system as foreign, and do not evoke a negative immune response.
- Production: Antibody screening and production is laborious and expensive, involving large-scale production of many different colonies in cell cultures. Because mAb synthesis involves all these different colonies, batch to batch variation, can be high. Performance can therefore vary. mAbs require weeks to months of development. Is also subject to contamination.
Benefit - Aptamers ✓
- Production: Aptamer synthesis is the product of simpler and controlled chemical reactions (SELEX) and is accurate with little to no variation from batch to batch. Aptamer synthesis is more cost effective, and can be automated - increasing the speed of the process greatly. Aptamers can be selected in hours. Chemical production also carries no risk of contamination.
-Target Potential: Targets must cause a strong immune response for antibodies to be produced. Does not recognize toxins, for example, because they do not trigger a strong reaction from the immune system.
-Target Potential: Aptamers can be targeted against toxins and other molecules that do not cause strong immune responses, as aptamer selection is not tied to the immune system. Aptamers can also bind to ions and other small molecules that antibodies cannot recognize including fragments and cell-surface targets - at no cost to affinity or specificity. Aptamers have the potential for "unlimited applications."
- Size: Antibodies are large molecules. This means they can resist filtration by the kidneys, leading to longer half-lives. However, their size prevents access to smaller areas.
- Size: Aptamers are small molecules.They are especially subject to kidney filtration, resulting in shortened half-lives. However, they can bind to smaller targets that antibodies cannot reach.
Benefit - Draw ✘
Although aptamers match antibodies property for property, and fill in antibody shortcomings, several crucial factors have prevented their widespread distribution. A combination of patents prevented initial spread, and this suppression of the technology has allowed antibodies to become well ingrained in the medical industry. Many in the industry are reluctant to tear themselves away from well-supported and effective antibodies for the risky and still relatively undeveloped aptamers.
In the future, as these patents expire, aptamer development will continue. Aptamers can fill a much-needed niche market in which treatments are found for diseases antibodies are cannot be not viable.
Although it is unlikely aptamers will ever completely replace antibodies in therapeutics, as there is an existing supporting infrastructure for antibodies and they work well in most situations, aptamers are an attractive solution in scenarios where antibodies' efficiency is limited.
For an example of an approved aptamer-based drug:
Read more about aptamer applications:
(Text Citation 4, Text Citation 5,Text Citation 14, Text Citation 36)
- Ability to be Modified: Antibodies cannot accommodate conjugates without negative consequences such as reduced activity. Conjugates are extra materials being added to the structure for therapeutic or other reasons.
- Ability to be Modified: Aptamers can readily accept conjugates. Further modifications to make up for shortcomings such as susceptibility to kidney filtration can also be easily introduced during synthesis.
- Patents and Distribution: There were no early patents on antibody research, leading to more widespread distribution and adoption since their introduction thirty years ago. A well-developed infrastructure exists to support antibodies.
- Patents and Distribution: Aptamers were protected by patents until very recently (2008 onward), limiting initial distribution. In that time, antibodies have become more well established. Many labs are reluctant to switch away from the "tried," if not necessarily "true" and reliable antibodies. In fact, aptamers are not included in curricula - information about aptamers must be actively sought out.
A Comparison
A comparison of 9 critical factors shows how aptamers can supplement Monoclonal Antibodies in disease-fighting:
Benefit - Draw ✘
Benefit - Antibodies ✓
Image Citation 17: Nucleases are enzymes that cleave at the bonds between nucleic acids.
Image Citation 17: Nucleases are enzymes that cleave at the bonds between nucleic acids.
Benefit - Aptamers ✓
Image Citation 18: Lab animal
Image Citation 18: Lab animal
Benefit - Aptamers ✓
Benefit - Aptamers ✓
Benefit - Aptamers ✓
Benefit - Aptamers ✓
Benefit - Antibodies ✓
Image Citation 19: Trademark of the United States Patent Office
Image Citation 19: Trademark of the United States Patent Office
Image Citation 20: The Kidney
Image Citation 20: The Kidney
Image Citation 21: A molecular toxin
Image Citation 21: A molecular toxin
Text Citation 43: Mycoplasms, common contaminants in mAb cultures
Text Citation 43: Mycoplasms, common contaminants in mAb cultures