Scientists recently introduced a groundbreaking technology called DNA-encoded alenomers to address the limitations of traditional aptamers. Aptamers are single-stranded nucleic acids that bind to specific targets like antibodies. However, their clinical potential is often hindered by their limited chemical diversity. While antibodies use twenty different amino acids, aptamers rely on only four nucleobases. Consequently, researchers have struggled to find aptamer-based drugs that possess the stability and affinity required for human medicine.

The Breakthrough of DNA-Encoded Alenomers

The development of DNA-encoded alenomers represents a significant leap in chemical biology. Unlike traditional aptamers, alenomers do not require compatibility with the enzymes used in natural selection processes. Instead, they utilize a branching DNA code that acts as a barcode for sequencing. This design allows scientists to incorporate non-nucleosidic components and highly diverse chemical groups into the binding sequence. Furthermore, researchers used an automated DNA synthesizer and split-and-pool methods to build a library containing approximately 300,000 unique members.

Expanding the Chemical Space for Therapeutics

The use of DNA-encoded alenomers allows for the exploration of an almost limitless chemical space. By removing the restriction of enzyme-compatible modifications, these molecules can achieve much higher binding affinities than standard aptamers. Additionally, these highly modified structures offer improved stability against enzymatic degradation in the human body. This advancement facilitates the discovery of protein-binding molecules that are more robust and effective. Consequently, this technology could accelerate the development of next-generation therapeutics for complex diseases like cancer and autoimmune disorders.

Frequently Asked Questions

What are alenomers?

Alenomers, or Aptamer-Like ENcoded OligoMERs, are highly chemically modified aptamers. They use an orthogonal DNA barcode to allow for sequencing without needing enzyme-compatible building blocks.

How do alenomers differ from traditional aptamers?

Traditional aptamers are limited to four similar nucleobases and must be compatible with selection enzymes. In contrast, alenomers can include diverse non-natural chemicals, significantly expanding their therapeutic potential.

Why is this technology relevant for clinical drug discovery?

This approach allows for the high-throughput screening of 300,000-member libraries. This leads to the identification of more stable and high-affinity protein binders that could become future clinical drugs.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or a professional endorsement. Always consult a qualified healthcare provider for specific medical concerns. Refer to the latest local and national guidelines for clinical practice.

References

1. Saliba D et al. Unlocking chemical diversity in aptamers with DNA orthogonal barcodes. Nat Chem. 2026 May 06. doi: 10.1038/s41557-026-02099-5. PMID: 42092186.


2. De Rochambeau D et al. Orthogonal DNA barcodes enable the high-throughput screening of sequence-defined polymers. ChemRxiv. 2022. doi:10.26434/chemrxiv-2022-v6pzl.


3. Nanni S et al. DNA-encoded chemical libraries: foundations and applications in lead discovery. PMC. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224712/