Oligonucleotide library design is one of the most critical steps in any drug discovery program. Generating an appropriate oligonucleotide library is the kick-off point to any drug discovery effort. The library needs to consider the project as a whole because the oligonucleotide chemistry, delivery method, species, and potential toxicity can be incorporated at this early stage to avoid the need for re-design later in your program. The use of artificial intelligence and machine learning platforms have greatly improved existing algorithms for delivering an oligonucleotide library with the greatest chances of success. Unlike small molecules, oligonucleotides do not have fast DMTA cycles with countless round of optimizations. Therefore, generation of an oligonucleotide library which is fit for purpose is essential for any drug discovery program.
ASO, siRNA, or miRNA Library Design Process
We custom design and specifically tailor oligonucleotide libraries for each of your drug discovery projects. Unlike basic design tools, you own the IP to the library designed by our experts. Just like no two projects are the same, no two oligonucleotide libraries should be the same.
A proprietary pipeline for generating and selecting the most promising oligonucleotide sequences with favorable drug-like properties.
Considerations for Oligonucleotide Design
It is important to perform in vivo studies in multiple species prior to clinical trials so a cross reactive oligonucleotide sequence can be beneficial to avoid generating a surrogate sequence or humanized model for pre-clinical development. Our in silico assessment allows for the simultaneous alignment of genomes from multiple species (rat, mouse, human, NHP) for the identification of oligonucleotides with cross-species potential.
As oligonucleotides work through Watson-crick base pairing, it is important to minimize the potential for unwanted off-target hybridization. Chemical modifications to the oligonucleotide sequence not only increase the binding affinity to the intended target, but it can also increase the occurrence of unwanted off-target effects. Our in silico design tools allow filtering of all candidate sequences to retrieve the ones with the least potential off-targets.
Nucleic acids can cause innate immune responses when delivered in vivo. There are known toxic motifs, especially in antisense oligonucleotides (ASOs) which can stimulate unwanted immune responses or toxicity. Our proprietary filtering parameters remove sequences which have these motifs so we can deliver an oligonucleotide library with safety in mind.
We have developed proprietary algorithms for the design of oligonucleotides for therapeutic applications. Our oligonucleotides libraries are custom designed and tailored to your specific project needs. By taking the time to understand your project requirements we are able to apply multiple filtering parameters to design an oligonucleotide library that is most optimal for your study.
