Technology Overview
Aptamer-ASO chimeras are innovative bifunctional oligonucleotide therapeutics that combine the high-affinity targeting of aptamers with the gene-silencing capabilities of antisense oligonucleotides (ASOs) [1]. This hybrid design enables precise delivery of ASOs to specific cells or tissues, enhancing therapeutic efficacy while minimizing off-target effects.
By leveraging aptamers’ ability to bind cell-surface biomarkers (e.g., receptors, proteins), the chimera selectively internalizes into target cells, where the ASO moiety modulates gene expression—either by degrading mRNA, blocking translation, or altering splicing [2]. This approach is particularly valuable for treating cancers, viral infections, and inflammatory diseases.
Key Advantages of Aptamer-ASO Chimeras
- Targeted Delivery: Aptamers direct ASOs to diseased cells, reducing systemic toxicity [3].
- Dual Functionality: Simultaneous target recognition (aptamer) and gene regulation (ASO) [1].
- Enhanced Cellular Uptake: Engineered aptamers improve intracellular delivery efficiency [4].
- Modular Design: Customizable for diverse targets (e.g., SARS-CoV-2, PD-L1, hematologic markers) [5].
Applications in Precision Medicine
1.Antiviral Therapy: Targeting SARS-CoV-2
A circular aptamer-ASO chimera suppressed SARS-CoV-2 replication and inflammation by targeting viral RNA and host factors [1].
2. Cancer Immunotherapy
PD-L1-targeting aptamer-ASO chimeras blocked immune checkpoint signals and downregulated oncogenes, demonstrating dual anti-tumor effects [4].
3.Hematologic Disorders
Aptamer-ASO chimeras delivered therapeutics to malignant blood cells with high specificity [5].
Design & Optimization Strategies
- Aptamer Selection: Cell-internalizing aptamers (identified via SELEX) ensure efficient ASO delivery [3].
- Linker Chemistry: Stable linkages (e.g., phosphodiester, circularized backbones) enhance chimera stability in vivo [1].
- Base Modifications: Chemical tweaks (2’-F, 2’-OMe) improve nuclease resistance and binding affinity [2].
Future Directions in Aptamer-ASO Therapeutics
Advances in aptamer-ASO chimeras are expanding RNA therapeutics into precision medicine, with ongoing research focusing on:
- Multivalent targeting for complex diseases [4].
- Combination therapies (e.g., with siRNA or CRISPR) [2].
- Clinical translation for unmet needs [5].
Our Aptamer-ASO Development Services
At BOC Sciences, we specialize in custom Aptamer-ASO design and optimization to accelerate your therapeutic development pipeline.
Our services include:
- Rapid aptamer discovery and selection from our proprietary library.
- Tailored ASO chemical modification for enhanced stability and potency.
- Scalable production and GMP-grade manufacturing.
- Preclinical validation support to fast-track your project toward regulatory approval.
Ready to Advance Your Targeted RNA Therapeutics?
Contact our expert team to explore how our Aptamer-ASO Chimera solutions can deliver your therapeutic payload with precision, efficiency, and reduced toxicity.
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References
- Efficient Targeted Delivery of Bifunctional Circular Aptamer-ASO Chimera to Suppress the SARS-CoV-2 Proliferation and Inflammation – Small (2023) DOI: 10.1002/smll.202207066
- Using aptamers for targeted delivery of RNA therapies – Molecular Therapy (2025) DOI: 10.1016/j.ymthe.2025.02.047
- Base-modified aptamers obtained by cell-internalization SELEX facilitate cellular uptake of an antisense oligonucleotide – Molecular Therapy – Nucleic Acids (2020) DOI: 10.1016/j.omtn.2020.11.016
- Anti-tumor effect of PD-L1-targeting antagonistic aptamer-ASO delivery system with dual inhibitory function in immunotherapy – Cell Chemical Biology (2023) DOI: 10.1016/j.chembiol.2023.10.010
- Aptamers and Antisense Oligonucleotides for Diagnosis and Treatment of Hematological Diseases – International Journal of Molecular Sciences (2020) DOI: 10.3390/ijms21093252