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Are Aptamers Better than Antibodies?

Currently, at NeoVentures, we believe that there is no concrete answer to the question if aptamers are better than antibodies. We have thoughts on why aptamers would be more useful in specific cases, but there just isn’t the same amount of literature available yet on the use of aptamers in therapeutic and diagnostic applications. We will outline our reasoning for each below:


Advantages of Antibodies

If it is desired that the binding of the therapeutic agent to a target molecule induces an immune response, then antibodies are clearly better for this than aptamers. This is because of how antibodies can induce the immune system response through their Fc-region, something that aptamers obviously do not have inherently in their structure. Additionally, due to the structure of aptamers (being DNA/RNA-based), an aptamer that does not have any modified bases will have rapid clearance through the renal system. This may limit the efficacy but does provide excellent pharmacokinetics. 

Advantages of Aptamers

At NeoVentures, however, we have developed aptamer selection strategies that enable us to identify aptamers that will or will not either induce endocytosis upon binding to specific transmembrane receptors, depending on the effect you are wanting. 

  • The induction of endocytosis is beneficial for the use of aptamers as a vector to introduce drugs into cells, in particular RNA drugs. 
  • The binding to transmembrane receptors without inducing endocytosis is beneficial for the use of aptamers to inhibit viral entry into cells. 

The use of aptamers as therapeutics for diseases where the existing immune response is undesirable, such as in auto-immune diseases such as lupus, or gastrointestinal disorders has not been sufficiently explored. This is an area where aptamers would have an advantage over antibodies. 


Advantages of Aptamers

Unlike therapeutics, aptamers should have an advantage over antibodies in diagnostics, in theory. This is because:

  • Aptamers are produced synthetically, with no need for recombinant cell production, no lot-to-lot variation 
  • Aptamers do not require chilling, and storage at RT for a year will not affect performance.
    • No refrigeration necessary
    • No ice is required for shipment
  • The small size of aptamers makes them attractive for applications in electrochemical-based detection.
  • The ability to identify aptamers for small molecules should increase the range of diagnostic targets. 
  • It is possible to drive selection for specificity to a higher degree with aptamers versus antibodies. 
  • The small size of aptamers makes them ideal for application in micro or nanofluidic devices. 
  • Aptamers can be characterized by qPCR analysis. 

However, there has not yet been an aptamer-based diagnostic test approved for medical diagnosis in Europe or the U.S. NeoVentures has commercialized diagnostic aptamer-based kits for food applications that did not require such approvals. The potential of aptamers in diagnostics has not yet been realized. 

Advantages of Antibodies

I think that a key difference between antibodies and aptamers represents the key constraint to the development of effective aptamer diagnostic devices. Antibody development is subject to a process termed Immune Tolerance. Every antibody that is produced in an animal is screened for its capacity to bind to self-targets. Even weak binding is not tolerated, all such antibodies are eliminated from production. Immune tolerance was not previously possible for aptamer development. We will provide more detail elsewhere in our FAQ, but counter selection against abundant targets within matrices, (HSA and IgG in the blood), mucins in saliva, and nasal fluid) is effective in removing aptamer sequences that bind strongly to these targets but relatively ineffective at removing sequences that bind weakly. Let’s discuss an example to provide greater clarity. 

Human serum albumin is present at an average concentration of 600 uM in plasma. If your target of interest is present at a concentration of 600 pM, then for every molecule of your target there are a million HSA protein molecules present. If an aptamer sequence binds to your target molecule with an affinity that is 1 million times greater than its binding to HAS, then there is a 50/50 chance that it will bind to one of your target molecules or to HSA. If the aptamers are less specific than this, then they will be saturated by binding to HSA and the detection sensitivity for your target will be lost in matrix. 

A New Approach to Immune Tolerance

This is why aptamers have not succeeded to date in diagnostic applications. At NeoVentures we have overcome this problem with our proprietary Neomer selection strategy. Learn more about Neomers and Immune Tolerance here.


Drug Discovery

Drug discovery involves high throughput analysis of the potential of candidate molecules to bind to target molecules and solicit a desired effect. Constraints within this area include:

  • Capacity to perform high throughput screens for successful creation of target molecules through cellular systems. 
  • Capacity for high throughput screens for candidate molecule interaction with target proteins
  • Capacity for high throughput screens for solicitation of desired therapeutic effect on a molecular basis.
  • Agnostic discovery of biomarkers for medical conditions for use as companion diagnostics in drug development 
  • Agnostic screening of pharmacokinetic effects in animal models 

We, NeoVentures and NeoNeuro, have developed a suite of proprietary solutions in coupling with our Neomer technology to address these needs. 

  • Generic high throughput screening platforms
  • Agnostic discovery of biomarkers (Aptamarkers – NeoNeuro)
  • Agnostic screening for pharmacokinetic effects (Aptamarkers – NeoNeuro) 

The details of these platforms are still confidential, but we are prepared to discuss how these could help your drug discovery efforts under confidentiality. Contact our team here to find out more.