Custom aptamers: 5 factors to consider before you begin
From drug screening to critical assay reagents and as targeted therapeutics, aptamers are increasingly being employed across the discovery and development pipeline.
Despite the large catalogues of antibodies, aptamers and alternative affinity ligands available, if you need to explore new targets, require batch-consistent reagents or have specific assay requirements that must be met, you may require a custom aptamer. Working with experts in aptamer discovery and development can speed your timelines and help to navigate potential project hurdles before they arise.
Here we take a look at some important factors to consider before beginning your custom affinity ligand development.
Overview
- The cost of ineffective affinity reagents
- Meeting or beating tight project timelines
- A specific affinity reagent that performs in the right assay environment
- Validated performance for reliable data outputs
- Downstream protection for your work
The cost of poorly validated affinity ligands
More than $17 billion USD is wasted annually in preclinical pharmaceutical research on ineffective biological reagents, including antibodies and aptamers. This cost includes:
- failed experiments
- having to purchase alternative reagents
- pursuing false biomarkers
- mistaken target ID stemming from inaccurate data
Antibodies are a major contributor to the reproducibility crisis. This crisis in the life sciences continues to highlight the inability to replicate key experiments with previously drawn conclusions from these antibody-based studies being shown as unfounded, due to target specificity issues.
Target specificity and ensuring that your selected antibody, aptamer or Optimer perform in the requisite assay matrix or environment is essential for confidence in your results. Working with a less-than-optimal affinity ligand may provide incomplete or inaccurate data, increasing the downstream risk to your project.
Considering the downstream manufacturing costs at the start of your project can prevent wasted research through market incompatible production prices. Make sure that the antibody, aptamer or Optimer you select for your development can be produced cost-effectively and efficiently at scale.
You can remove this issue by making sure that your custom aptamer or antibody is fit-for-purpose and expertly discovered, developed, and validated. Taking these steps will accelerate your pipeline by improving research efficiency and transitioning projects to the trials phase faster. Consulting with experts in custom development before beginning your project can provide the confidence that the custom reagent you receive will be specific and robust enough to progress your research.
Meeting or beating tight project timelines
Unnecessary reagent expenditure may not be appreciated by your accountant, but the highest unaccounted cost to life science research is human capital expenditure. This includes time spent researching, designing, performing and analysing experiments.
Developing your own antibodies or aptamers in-house is highly laborious and time-consuming, with most projects taking ~9 months and still delivering inadequate results. The majority of commercial antibody development takes months for each ligand and all too often yield poor specificity, necessitating further engineering efforts that may never meet the required specifications.
To avoid unnecessary research delays, working with a trusted partner to develop the right aptamer or Optimer reagent for your needs can speed your timelines, accelerating your route to market. Before you begin to work with a custom affinity ligand developer, it is vital to make sure they understand and can work to your project timelines. Without this you risk unnecessary delays and you could miss those important milestones.
A specific affinity ligand that performs in the right assay environment
Your project will define the specific Optimer, aptamer or antibody that you need. Particular binding characteristics, target selectivity or cross-reactivity, tolerance of different matrices, in vivo half-life and many more attributes will be required to meet different project goals and all must be taken into account at the outset.
Making sure that your development partner has a complete understanding of your project and what you want to achieve can help them to map out the required profile of the custom Optimer, aptamer or antibody, and influence the strategy of the discovery campaign for your ligand. Your development partner should show an interest and ask for these details when you are establishing the project, as they can make the difference between advancing your research or adding to your avoidable experimental expenditure.
Rely on the knowledge of your Optimer, aptamer or antibody development partner. We know from our own work at Aptamer Group that bringing our team’s expertise in working with a wide range of assays and targets can help to navigate any downstream stumbling blocks for our partners.
Validated performance for reliable data output
Once your custom affinity ligand has been developed, the right validation of your ligand is imperative. This will give you confidence that the ligand binds to the target you need, in the assay environment that you need, shows no cross-reactivity and that any data you generate using this Optimer, aptamer or antibody is reliable and can be easily interpreted.
Multiple methods exist to validate affinity ligands, from simple target binding and KD analysis to evaluating application-specific performance. If your custom Optimer, aptamer or antibody requires extensive validation or you need a tailored assay development service, working with partners that support such studies can help to provide a complete data package to fast-track your research.
Downstream protection for your work
Following all your hard work in R&D, bringing a product to market that relies on an Optimer, aptamer or antibody or incorporating a new process into your workflow that needs this affinity ligand, means you need security of supply and assurance on batch consistency. These are essential to prevent delays in your workflow or supply to market.
Security of supply consists of a number of critical factors, including the availability and cost efficiencies of production, a known sequence to allow de novo synthesis should your Optimer, aptamer or antibody be lost or damaged and the option to work with multiple suppliers to ensure sufficient availability.
The batch-to-batch consistency of your reagent is crucial to prevent extensive standardisation work or the loss of your assay or research output through affinity ligand batch inconsistencies that result in irreproducible data.
Another important consideration is the potential scalability of your selected Optimer, aptamer or antibody. Scaling protein production processes that rely on mammalian cell expression systems are non-linear, require extensive bioprocessing knowledge and can cause delays in antibody development. However for oligonucleotide-based affinity ligands, such as aptamer and Optimers, well-established scalable production chemistries are in place that ensure simple scalability and excellent batch consistency through solid phase synthesis.
Finally, if you are considering shipping products globally or storing products for extended periods you could consider the shelf-life, storage requirements and the requirements for cold-chain supply all of which may reduce the longevity of the product and increase logistical requirements.
We have a depth of experience in delivering custom Optimers to the most challenging targets for use in a wide range of applications, and offer end-to-end expert consultation on all projects. Our robust processes and automated platforms ensure rapid development and delivery of the highest-performance affinity ligands.
For further information please get in touch.
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