Aptamer-Drug Conjugates Design

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What is Aptamer-Drug Conjugates?

Aptamer is a functional nucleic acid that can recognize and bind target substances with high specificity and affinity, and can be obtained by Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technique screening, with sequence length mostly between 15 and 60 bases.

Aptamer-drug conjugates (ApDCs) are a form of drug conjugates that uses a structured oligonucleotide sequence (aptamer) as the target molecule. Aptamers are referred to as "chemical antibodies" and have similar targeting and target binding capabilities to antibodies. Aptamers can be loaded with therapeutic cargoes (drugs) such as chemotherapeutics, photosensitizers, photothermal agents, immunotherapeutics, RNA, enzymes, or even bifunctional combination molecules (e.g. PROTAC, LYTAC).

Aptamer-Drug Conjugates Design

  • Features of ApDCs using aptamer as a targeting molecule:

(1) Wide range of targets: Targets include metal ions, amino acids, nucleotides, growth factors, proteins, viruses, bacteria, living cells, and living organisms, etc.

(2) High affinity and high specificity: Aptamers with high specificity that recognize only the target molecule but not other molecules can be obtained during the screening process.

(3) Good stability: Aptamers have good chemical stability and thermal stability, and are also convenient for preservation and transportation. In addition, after special modification, the aptamer has better stability and longer half-life.

(4) Low immunogenicity: The aptamer has low molecular weight and small size, which can easily cross the tissue barrier and reach the site of action quickly, and also be easily cleared by the metabolic organs in the body, so it has low immunogenicity and toxicity.

(5) Easy to prepare and modify: Aptamers are synthesized rapidly and in large quantities in vitro by chemical synthesis methods such as DNA synthesis technology, PCR technology or RNA in vitro transcription, and are reproducible from batch to batch.

Why Aptamer-Drug Conjugates?

  • Aptamer-PROTAC Conjugates

The development of proteolysis-targeting chimeras (PROTAC) is a promising strategy for targeted protein degradation. However, PROTAC heterobifunctional molecules are usually limited by poor membrane permeability, low in vivo potency, and inhomogeneous distribution. Therefore, aptamer-PROTAC conjugates may serve as a novel strategy. By coupling PROTAC to aptamers through cleavable linkers, aptamer-PROTAC conjugates could show improved targeting ability with the potential to enhance target protein degradation and reduce off-target toxicity compared to unmodified PROTAC.

  • Aptamer-LYTAC Conjugates

Lysosome-targeting chimera (LYTAC) is a promising technology to extend the scope of target proteins to extracellular targets. However, LYTACs have high uncertainty in number and location, high molecular weight and low internalization efficiency. Aptamer-LYTAC conjugates could serve as a novel solution to avoid these problems. The specific degradation of extracellular and membrane proteins could be achieved by binding the aptamer to tri-GalNAc. It is worth mentioning that aptamers have the advantage of easy synthesis and low molecular weight. Aptamer-LYTAC conjugates are expected to expand the use of aptamers and provide new insights into targeted protein degradation.

Services of Aptamer-Drug Conjugates Design

  • Aptamer synthesis and screening
  • Conjugation chemical methods (optional)
  • Aptamer-drug conjugates synthesis and characterization
  • Linker design and optimization

Why BOC Sciences?

  • Optimized synthesis routes for conjugates
  • Extensive expertise in various cross-link modifications and conjugation reactions
  • Multiple analysis methods such as HPLC, MS, NMR, affinity chromatography, size exclusion chromatography
  • Quality management through all processes of conjugates synthesis, purification and analysis
  • Assist customers from design to delivery

* PROTAC® is a registered trademark of Arvinas Operations, Inc., and is used under license.

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