Advanced| neoaptamers https://neoaptamers.com/es/category/advanced/ Neoventures Biotechnology Inc. Mon, 13 Apr 2026 19:49:02 +0000 es hourly 1 https://wordpress.org/?v=7.0 https://neoaptamers.com/wp-content/uploads/2024/07/cropped-NeoVentures-Biotechnology-Square-Logo-No-Text-1-32x32.png Advanced| neoaptamers https://neoaptamers.com/es/category/advanced/ 32 32 How We Avoid Self-Recognition with Aptamers https://neoaptamers.com/es/avoiding-self-recognition-with-aptamers/ Wed, 16 Nov 2022 19:19:47 +0000 https://neoaptamers.com/?p=3101 Antibody Binding vs. Aptamer Binding The immune system has developed very effective screening methods for eliminating antibodies that bind even weakly to self targets such as serum albumin and IgG. Aptamer selection is done outside the body, on the bench which provides many advantages but implicit immune tolerance in selection is not one of them.   … Leer más »How We Avoid Self-Recognition with Aptamers

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]]> Antibody Binding vs. Aptamer Binding

The immune system has developed very effective screening methods for eliminating antibodies that bind even weakly to self targets such as serum albumin and IgG. Aptamer selection is done outside the body, on the bench which provides many advantages but implicit immune tolerance in selection is not one of them. 

Diagram describing self-recognition in aptamers

 

Counter Selection

Counter selection against off-targets has been the only way to produce aptamers that will not bind to other targets in bodily fluids. SELEX is based on the use of 1E15 sequences derived from 1.2E24 possible sequences. This means that every selection is based on a new set of sequences. It has not been possible to test the same starting set of sequences on different targets. 

Counter selection is very effective against those sequences that bind tightly to the off target. It is not effective in removing those sequences that bind weakly. To be clear, counter selection is not as effective or as thorough as immune tolerance. 

Does this really matter? Unfortunately, yes. Abundant proteins like serum albumin are present in blood at an average concentration of 600 uM. If we are trying to detect targets at much lower concentrations even weak counter-binding will result in saturation of aptamer binding to serum albumin. 

Our Solution

NeoVentures has overcome this problem with our new Neomer aptamer selection method. The method involves application of an average of 1,000 copies of each of the same 4.29 billion sequences to every target. This means that we can identify all the sequences that bind even weakly to abundant proteins and remove them as candidates for your target. In essence we have created an in-silico alternative to avoiding self-recognition. This is a game changing innovation which will definitely lead to better performance of aptamers in diagnostic applications. Read more about Neomer in our blog.

To learn more about what this means for your ability to use aptamers to overcome problems in your diagnostic portfolio, contact our team today. 

Follow us on LinkedIn to get notified every time we release new information on Neomer.

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]]> Can Aptamers Bind to Sugar Molecules? https://neoaptamers.com/es/can-aptamers-bind-to-sugar-molecules/ Wed, 09 Nov 2022 16:35:42 +0000 https://neoaptamers.com/?p=3090 Did you see our poll on LinkedIn? If not, check it out here! Our answer to this poll will be short and sweet: Sugars are molecules that have a generic formula of CnH2nOn. They can be described as polyhydroxy compounds containing one ether bond. Most sugars are optically active, and this comes from the presence… Leer más »Can Aptamers Bind to Sugar Molecules?

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]]> Did you see our poll on LinkedIn? If not, check it out here!

Our answer to this poll will be short and sweet:

Sugars are molecules that have a generic formula of CnH2nOn. They can be described as polyhydroxy compounds containing one ether bond. Most sugars are optically active, and this comes from the presence of asymmetrically substituted carbons in the sugar. In an aqueous environment the rings can take two forms. During the formation of the ring if the hydroxy group is trapped above the ring it will be the Beta form, if it is trapped below the ring it will be alpha. The two forms will slowly interconvert until equilibrium is established.

We have tried to identify aptamers for monosaccharides and disaccharides but have not been able to identify aptamers that bind well to sugar molecules. This could be because of the abundance of negative charges on sugars (hydroxyl groups) and because sugars are in constant flux between shapes, both in and out of the chair form, and the hydroxyls spinning such that the distance between them is not constant.

For aptamer selection to be effective, there needs to be a fixed distance between charges. If the charges are changing in space, then all aptamer sequences are equally good at binding to them. If charges are fixed because of double bonds in the target molecule, or even better, double bonds in a ring, then the charges are not rotating and the distance between them is fixed. The more defined the solution space is physically for a target the more successful the aptamer selection will be.

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]]> Announcing The Future of Aptamers: Neomers https://neoaptamers.com/es/announcing-the-future-of-aptamers-neomers/ Thu, 06 Oct 2022 20:59:35 +0000 https://neoaptamers.com/?p=3045 The use of the traditional SELEX method for aptamer development has led to the identification of aptamers that bind to a wide diversity of targets. However, there has been limited success with aptamers in therapeutic and diagnostic applications.  A key advantage of aptamer development over antibody development is that it is performed in vitro outside… Leer más »Announcing The Future of Aptamers: Neomers

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]]> The use of the traditional SELEX method for aptamer development has led to the identification of aptamers that bind to a wide diversity of targets. However, there has been limited success with aptamers in therapeutic and diagnostic applications. 

A key advantage of aptamer development over antibody development is that it is performed in vitro outside of living systems. This is also a disadvantage because antibodies are screened after development for their capacity to bind, even weakly, to self-targets in blood. Traditional aptamer selection does not have this step. The capacity to screen by using counter selection is useful, but ultimately not sufficient because it does not effectively remove aptamers that bind weakly to self-targets.

 

Why is This a Problem? 

Serum albumin is present in blood at a concentration of 600 uM. Most abundant biomarkers are present at concentrations ranging from fM to low nM. This means that for every target molecule present, there are millions, or billions, of serum albumin molecules also present. Even very weak binding to serum albumin will saturate the aptamer, leaving none left to bind to the target, even if the aptamers bind to the target with very high affinity. 

Binding between ligands and receptors is often misunderstood. These are never fixed binding events. These are associations that are on and off in microseconds. Thus, binding should always be thought of as an equilibrium. As such the concentration of what a ligand is binding to is equally important to the strength of binding. 

 

The Solution

At NeoVentures, we have always been leaders in developing aptamers as commercial products. With our invention of the Neomer method of aptamer development we have not only overcome the traditional problem of aptamers lacking specificity, but we have done so in such a profound as to change the very basis of aptamer science. 

This is a bold statement, but we now have the data to back it up. The Neomer method involves the use of a library of the same 4.29 billion sequences for every selection. We have replaced the need for reiterative cycles of selection in SELEX by starting with an average of 1,000 copies of each sequence in this library rather than 1. We can characterize the level of binding of a target molecule on all 4.29 billion sequences in a single selection round, followed by a clever trick we employ for NGS analysis. We have characterized the fingerprint of HSA and IgG on this library and are able to ensure that any sequence that binds to these proteins even weakly is removed as a candidate for your target molecule. 

 

The Future of Aptamers

The power of this new approach should be apparent to anyone involved in diagnostics or therapeutics. This means that now we can:

  • Identificar aptámeros que se unen al mismo epítopo en varias proteínas.
  • Identificar aptámeros que distingan entre diferentes isoformas de una proteína.
  • Junto con nuestra plataforma exclusiva FRELEX, Neomers permite la identificación definitiva de metabolitos solubles. 

We want to share access to the Neomer platform as broadly as possible. Thus, while we now provide the platform as the basis for our fee-for-service business, we are also providing the Neomer library on a license basis. We will provide you with our library, you perform the selection yourself, even the NGS analysis and we will analyze your data against our database of protein and metabolite fingerprints on the same library and provide you with the results. We are doing this while maintaining our commitment to your ownership of the aptamers, royalty free. 

To learn more, get in touch with our team.

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]]> Why Do Antibodies Perform Better in Matrices than Aptamers? https://neoaptamers.com/es/antibody-specificity/ Wed, 14 Sep 2022 15:22:49 +0000 https://neoaptamers.com/?p=2973 The clear winner of our poll on antibody specificity was that antibodies have evolved to ignore HAS/IgG. I struggle with this, as I think it is too simple. Really, the way that antibodies rearrange to detect foreign antigens is open; there are no barriers to antibodies developing against self proteins. We probably should have used… Leer más »Why Do Antibodies Perform Better in Matrices than Aptamers?

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]]> The clear winner of our poll on antibody specificity was that antibodies have evolved to ignore HAS/IgG. I struggle with this, as I think it is too simple. Really, the way that antibodies rearrange to detect foreign antigens is open; there are no barriers to antibodies developing against self proteins. We probably should have used a different term than Chckpt Inb (checkpoint inhibition) as the second option, but this is the essence of why antibodies work well in matrices. Antibodies that develop to bind to self-targets within a biological matrix, such as human serum albumin or the Fc regions of IgG’s, undoubtedly do arise, but they are eliminated as dangerous. There are two systems, gratis – open development of antibodies against any target, and a counter-balancing system that detects and weeds out antibodies that bind to self proteins. 

This counter balance system is what is missing from aptamer selection. We can perform counter selection against the matrix, but this only effectively eliminates those aptamers that bind really strongly to a matrix component. Counter selection against serum albumin should theoretically be performed at the concentration that serum albumin is present in blood (600 uM). We do this by using serum directly in counter selection with our FRELEX approach, or by immobilizing all of the protein in blood on UltraLink resin. 

Our new Neomer selection platform represents the addition of a counter-balancing system to weed out all aptamers that bind, even weakly, to counter targets. With the Neomer system we are able to catalogue aptamer sequences that bind to dominant counter targets like HSA and IgG, and remove them as candidate sequences. 

To learn more about the Neomer aptamer selection method please: 

Check out our lecture

Get in touch on our website

Or reach out by email to info@neoventures.ca

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]]> How We Avoid Immobilizing Targets with FRELEX https://neoaptamers.com/es/frelex-advantages/ Wed, 27 Jul 2022 12:37:44 +0000 https://neoaptamers.com/?p=2874 Designing aptamers for specific targets needs to be done in a way that ensures you are selecting the aptamers that bind to your target while easily getting rid of those sequences that do not. Typically, this is done by immobilizing the target so that aptamers that bind will stick, while those that do not bind… Leer más »How We Avoid Immobilizing Targets with FRELEX

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]]> Designing aptamers for specific targets needs to be done in a way that ensures you are selecting the aptamers that bind to your target while easily getting rid of those sequences that do not. Typically, this is done by immobilizing the target so that aptamers that bind will stick, while those that do not bind get washed away. The big disadvantage to immobilizing targets is that part of the target is removed from selection due to it being attached to the solid support. This is problematic with every target, from small molecules (entirely removing epitopes for binding) to large proteins (potential to affect folding). We have been able to solve this problem by developing the FRELEX platform, which allows for separation of bound aptamers to the target from those that are not bound in a way that neither the target nor aptamer is immobilized on a surface.

 

Qué es FRELEX?

The FRELEX platform utilize a library of random short oligonucleotides on a gold chip. These short oligonucleotides act like a ‘lawn’ that the aptamers can ‘sit’ on by hybridization via Watson-Crick pairing. We first select for the aptamer sequences that sit on this lawn without the target being there. The sequences that bound to the surface are removed and then incubated with the target and reintroduced to the lawn on the gold chip. If the aptamer binds to the target, it will not be able to sit on the lawn of oligonucleotides and we are able to isolate those sequences away from the aptamers that are still sitting on the lawn, and therefore not busy binding to the target.

 

 

This approach allows us to select for epitopes on the entire target and not have to worry about selecting aptamers that are non-specifically binding to the immobilization surface used. We continue to use FRELEX to select aptamers for small molecules and proteins to ensure that we are designing the best aptamers for the diagnostic or therapeutic application.

 

To learn more about the development and ideal applications of FRELEX, get in touch with our team.

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]]> Aptamer Structure Prediction https://neoaptamers.com/es/aptamer-structure-prediction/ Thu, 07 Jul 2022 15:41:25 +0000 https://neoaptamers.com/?p=2804 The relationship between structure and function is pretty obvious in a lot of engineering projects. Clearly the same is true for aptamers. The functionality of an aptamer is based entirely on it’s structure. In this series of blogs we are going to reveal how we perform meta-analysis of aptamer structures as a basis for identification… Leer más »Aptamer Structure Prediction

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]]> The relationship between structure and function is pretty obvious in a lot of engineering projects. Clearly the same is true for aptamers. The functionality of an aptamer is based entirely on it’s structure. In this series of blogs we are going to reveal how we perform meta-analysis of aptamer structures as a basis for identification of candidate sequences and as a means of improving selected sequences. 

Our ever improving ability to perform deep data analysis of aptamer structures is one of the keys that makes NeoVentures the top aptamer development company globally. 

How do we do this? 

Meta-analysis of aptamer sequences is relatively straightforward. Sequences are strings of information and as such thousands of sequences can be compared in a single run. The key to doing the same with structures is to reduce the structure information to strings of information. We have software that enables us to define the state of a nucleotide in terms of it’s structural status. This is entered as a code and rendered as a string. 

We then use a suite of in-house software that enables us to predict thousands of these structures from a data set and compare them for similarities. We overlay this analysis on the more traditional sequence analysis to develop an understanding of what effect a selection has had on aptamer structure. 

Our capacity for meta-analysis of aptamer structures in coupling with meta-analysis of sequences allows us to change the way we choose candidate sequences for further analysis. In the past we chose individual sequences based on the effect of selection of different targets on them. Now, we are able to consider the selected aptamers as a whole and determine what structures are being selected. We are then able to choose representatives of these selected choices. 

At NeoVentures, we perform this analysis on all of our aptamer projects. We are now ready to apply our capacity in this regard to your aptamer selection data and help you choose candidate sequences. Please contact us for a quote and a discussion of how this service could help you identify better aptamers.

Request a FREE consultation.

Or send us an email: info@neoventures.ca

In the next blog we will discuss the power of structural analysis applied to our Neomer method for aptamer selection.

 

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]]> How Does Chemical Reversibility Impact Commercial Aptamer Diagnostics https://neoaptamers.com/es/the-concept-of-chemical-reversibility-and-implications-for-commercial-aptamer-diagnostics/ Mon, 16 May 2022 14:37:58 +0000 https://neoaptamers.com/?p=2545 This blog starts with a portrait of Claude Louis Berthollet (1748 – 1872), who was the first to demonstrate and elaborate on the concept of chemical reversibility. As an aside, it should be noted that he accompanied Napoleon to Egypt and, along with Joseph Fourier, investigated means of converting the sodium carbonate found there into… Leer más »How Does Chemical Reversibility Impact Commercial Aptamer Diagnostics

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]]> This blog starts with a portrait of Claude Louis Berthollet (1748 – 1872), who was the first to demonstrate and elaborate on the concept of chemical reversibility. As an aside, it should be noted that he accompanied Napoleon to Egypt and, along with Joseph Fourier, investigated means of converting the sodium carbonate found there into gunpowder. The concept of chemical reversibility is simple enough. The relation between the on rate and the off rate of reactions determines the direction that a chemical reaction proceeds in. 

The implications, however, are profound. When two molecules bind to each other this is a reversible reaction. Especially as is the case with aptamer and antibody interaction, the binding event does not involve the formation of a covalent bond. When we describe the affinity of these binding reactions we use the terms on rate (k on) and off rate (k off). Note that these terms are defined as concentration per unit time (M-1 sec-1). This means that individual molecules are forming complexes and disassociating from such complexes on a microsecond scale. Binding affinities measured in terms of k on and k off represent the proportion of the molecules that are in either state at a given time. Non-covalent binding, even strong non-covalent binding, is not ever a fixed event. It is a measurement of a dynamic state. 

I said above that the implications are profound. Why does it matter that we are actually measuring a dynamic state? It matters in terms of the design of commercial products for several reasons.

  1.  Every time that there is a wash in a diagnostic test, there will necessarily be a loss of bound complex. Dynamic states are governed by the mathematical rules of equilibrium, and these rules must be obeyed. If all the free, unbound target is removed from a system, then a portion of the bound target must become unbound in order to satisfy the equilibrium.  
  2. The volume of solution that the bound complex is present in determines the proportion that is bound versus the proportion that is unbound. The lower the volume, the smaller the off-state room and the higher the proportion bound. 
  3. The farther a system is from equilibrium the more noise there will be from measurement to measurement. 

At NeoVentures we love mathematical models of systems. When we interact with our clients on projects we apply our understanding of the binding coefficients of aptamers to the development of models of diagnostic systems. This then enables us to understand how to achieve the performance that we need. 

The discovery of the rules of chemistry by Lavoisier, Bertholett, Priestly and many others was an incredible feat of human intellect. It just makes sense to stand on the shoulders of these giants as we create the next generation of diagnostic products.

 

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]]> How We Overcome Process Bias with Neomers https://neoaptamers.com/es/advantages-of-the-neomer-selection-process-overcoming-process-bias/ Wed, 27 Apr 2022 15:31:35 +0000 https://neoaptamers.com/?p=2276 This is the first of several blogs we will share on our new Neomer process. The image above can be compared to a dilemma in traditional aptamer selection: are the aptamers that are enriching the product of the selection process (I would vote for the wine glass for this representation), or the product of bias… Leer más »How We Overcome Process Bias with Neomers

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]]> This is the first of several blogs we will share on our new Neomer process. The image above can be compared to a dilemma in traditional aptamer selection: are the aptamers that are enriching the product of the selection process (I would vote for the wine glass for this representation), or the product of bias of the selection process (the faces impinging on the wine glass), and how do we tell sequences apart? 

There are many possible reasons for process bias on aptamer selection, but probably the most clear is the potential for PCR bias. This is evinced in at least two ways in sequencing data, a) aptamers that show high copy number enrichment over selection rounds but little or no binding to the target, and b) aptamers that show high copy number enrichment on both positive and negative selections. The latter observation leads to non-consideration of these aptamers but still it is annoying, why are they doing this? 

It is clear that the more secondary structure in an aptamer the less well it is amplified. This often runs counter to optimum aptamer selection as strong, stable secondary structure is often a defining feature of good aptamers. PCR bias in aptamer selection is manifested as an exponential factor that is multiplied across selection rounds. Binding affinity and specificity is only a linear factor and thus can be easily overcome by PCR bias. 

In our Neomer aptamer discovery method we overcome this problem in two ways. 

One, we can perform as little as a single round of selection, thus differences in PCR efficiency are not accumulated. Two, given that we can start selection with different aliquots of the identical naïve starting library, we can run a negative control selection without target and use this to normalize for all selection effects on individual aptamer frequency, including PCR bias. 

In our next blog we will discuss the statistical basis of Neomer analysis, and how this adds strength to the removal of bias and enables identification of desirable aptamers from the selection data. With the Neomer method we can parse the wine glass and most importantly, the wine within it from artefacts that were part of the process.

 

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]]> Denaturation of Aptamers for Commercial Applications? https://neoaptamers.com/es/denaturation-of-aptamers-for-commercial-applications/ Mon, 04 Apr 2022 15:23:13 +0000 https://neoaptamers.com/?p=1999 The phoenix of mythology arises from the ashes of its predecessor. This seems like a very intriguing phenomena, but strikes me as difficult to control in a commercial application. Yet, we keep getting asked whether this is necessary for aptamers to work. Do aptamers need to be denatured and then allowed to renature so that… Leer más »Denaturation of Aptamers for Commercial Applications?

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]]> The phoenix of mythology arises from the ashes of its predecessor. This seems like a very intriguing phenomena, but strikes me as difficult to control in a commercial application. Yet, we keep getting asked whether this is necessary for aptamers to work. Do aptamers need to be denatured and then allowed to renature so that they will bind to a target? 

Our answer at NeoVentures is that if this is necessary for a given aptamer, then this aptamer should be discarded and you should find one that does not require denaturation prior to use. This is simply impractical for a commercial product with the aptamer, either a therapeutic or diagnostic application. At NeoVentures we do denature our libraries during the selection process. We do this at this stage because there are a large assortment of different sequences present that could hybridize to each other. We then snap cool to enhance individual shapes. 

In all  our binding assays we do not denature and renature. If an aptamer requires this then it will be observed as not working in our assays and discarded. Aptamers that require this are a non-starter for actual commercial use. 

An aptamer that requires denaturation and renaturation in order to bind is a strong warning sign. Every aptamer is in flux among shapes at whatever temperature it is at (except 0 Kelvin). When we truncate and optimize aptamers we stabilize the shape that is responsible for binding, but still some flux is unavoidable. If an aptamer requires denaturation and renaturation to work this indicates that it is a sub-optimal shape (from a free energy point of view) that is responsible for the aptamer binding. The sub-optimal shape is likely more prevalent at an early stage of renaturation, and reduces in prevalence over time. We have observed aptamers that will work the first day that they are solubilized and then not work a few days or a week later (again, these would be discarded). For commercial applications (and really, why else are we doing this…) aptamers need to be able to stably perform for up to a year. 

There are many beautiful concepts like the phoenix in mythology and I like to think that the aptamers we are producing for our clients are works of art, but works of art often only appreciate in value after the demise of the artist. The real beauty of a commercial aptamer application is robustness and simplicity. 

Next week’s blog: an introduction to a new method of aptamer selection, “Neomers”.

 

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