Custom Oligonucleotide-Small Molecule Conjugation Service
Are you encountering difficulties with issues like enzymatic breakdown, inadequate cellular absorption, and swift excretion in your oligonucleotide-based therapeutic development? Creative Biolabs's Custom Oligonucleotides-Small Molecule Conjugation Service helps you address these issues with advanced oligonucleotide modifications and precise conjugation strategies.
Fig.1 Four biological barriers preventing activity of therapeutic oligonucleotide.1
How Can We Assist Your Project?
Oligonucleotide-small molecule conjugates represent a promising category of therapeutic agents, combining the precise targeting of oligonucleotides with the potent pharmacological benefits of small molecules. This approach enhances selectivity, precision, and delivery efficiency while minimizing off-target interactions. Creative Biolabs offers customized solutions to address the challenges inherent in oligonucleotide-based therapies, ensuring the delivery of high-quality conjugates that improve in vivo efficacy.
Fig.2 General molecular structure of oligonucleotide-small molecule conjugate.1
Our Services:
- Conjugation to various small molecule ligands (e.g., targeting ligands, fluorescent dyes, cytotoxic agents).
- Site-specific conjugation using a range of linker chemistries.
- Custom synthesis of modified oligonucleotides for conjugation.
- Analytical and purification services for oligonucleotide conjugates.
Workflow:
Creative Biolabs employs a streamlined and efficient workflow to ensure the successful completion of your oligonucleotide-small molecule conjugation project. Our service involves several key steps.
| Steps | Description | Expected Outcome |
|---|---|---|
| Project Consultation and Design | We begin with a detailed consultation to understand your project goals, oligonucleotide and small molecule properties, and any specific requirements. Based on this, our expert team designs a customized conjugation strategy. | Finalized project plan and conjugation strategy. |
| Oligonucleotide Modification (if necessary) | If the oligonucleotide requires modification to introduce a functional group for conjugation, we perform the necessary chemical modifications. | Modified oligonucleotide ready for conjugation. |
| Conjugation Reaction | We perform the conjugation reaction under optimized conditions to ensure efficient and specific coupling of the small molecule to the oligonucleotide. | Crude conjugate mixture. |
| Purification and Analysis | The crude conjugate is purified using appropriate techniques, such as HPLC, gel electrophoresis, or other chromatographic methods, to remove unreacted starting materials and byproducts. The purified conjugate is then analyzed via mass spectrometry (MS) and HPLC. | Highly purified and characterized oligonucleotide-small molecule conjugate. |
| Quality Control and Delivery | The final conjugate undergoes rigorous quality control testing to ensure it meets the highest standards of purity, stability, and integrity. Upon successful completion of quality control, the final product, along with a comprehensive report, is delivered to the client. | Final product and comprehensive report. |
Required Starting Materials:
- Oligonucleotide sequence and specifications (including any existing modifications).
- Small molecule structure and specifications (including any functional groups available for conjugation).
- Project-specific requirements, such as desired conjugation site, linker type, and target application.
Final Deliverables (comprising two standardized components):
- Purified conjugate product in lyophilized form.
- Accompanying analytical documentation includes mass spectrometry and HPLC verification, confirming the identity and purity of the conjugate.
Estimated Timeframe:
Project timelines range from 4-8 weeks post-order setup, contingent upon structural complexity factors including modified nucleotide content (e.g., LNA/GNA incorporation), linker chemistry requirements (e.g., disulfide or PEG-based spacers), and synthesis scale (micrograms to milligrams). Accelerated schedules apply to standard phosphorothioate backbone configurations and require no special modifications.
Why Choose Us?
- Expertise: Our researchers wield specialized expertise in nucleotide engineering, molecular chemistry, and bioactive crosslinking. By tracking emerging advancements—from dynamic covalent chemistry to spatial-omics integration—we deliver solutions calibrated at scientific frontiers.
- Precision Tailoring: Each project's DNA demands bespoke orchestration. We co-design conjugation blueprints detailing anchor site selection and linker stereochemistry. Your molecular vision determines the details of each step of the conjugation.
- Quality Assurance: The purity, stability, and integrity of your conjugates are secured by our adherence to the highest quality control standards. Our advanced laboratory infrastructure and stringent assurance processes yield dependable and consistent results.
- State-of-the-Art Technology: Creative Biolabs utilizes advanced technologies, including high-resolution MS and HPLC, to characterize and ensure the quality of the final product.
- Proven Success: Our clients experience significant improvements in their research outcomes.
Case Study
Explore our success stories through a detailed case study.
Case 1: We have designed and synthesized custom-modified nucleotide chains for our client, and successfully conjugated them with small molecules.
- Mass Analysis: Molecular weight error ≤0.1%
- HPLC Analysis: Conjugate purity >99%
Customer Reviews
S***y:
"Using Creative Biolabs's Custom Oligonucleotides-Small Molecule Conjugation Service in our research has significantly improved the targeted delivery of our therapeutic oligonucleotides to disease sites."
[7 Weeks]
C***s:
"Creative Biolabs's conjugation expertise has significantly facilitated our in vivo studies by enhancing the stability of our oligonucleotide-based drugs against enzymatic degradation."
[6 Weeks]
V***n:
"Our oligonucleotide conjugates ordered from Creative Biolabs significantly enhanced cellular uptake, which helped us achieve promising results in our gene therapy research."
[10 Weeks]
FAQs
1. Q: What molecular payloads are compatible with oligonucleotide conjugation?
A: Creative Biolabs supports covalent attachment of diverse bioactive payloads, including targeting moieties, fluorophores, pharmacologically active compounds, and specialized functional groups. Selection depends on desired conjugate functionality and application parameters. We recommend consultation with our scientific team for target-oriented design.
2. Q: What chemical coupling strategies are implemented?
A: We utilize multiple chemical approaches: copper-free click reactions, carbodiimide-mediated amidation, and engineered enzymatic ligation systems. Our technical team selects the most appropriate protocol based on oligonucleotide modification patterns and payload reactivity profiles. Request detailed methodology documentation for your specific case.
3. Q: What analytical validation is performed on final conjugates?
A: Our quality assurance process incorporates analytical verification through HPLC and MS detection. Each conjugate batch provides comprehensive Certificate of Analysis documentation.
4. Q: What determines synthesis project timelines?
A: Operational timelines (standard 4-8 weeks) are influenced by synthetic complexity (modified bases, sensitive functional groups), purification challenges (hydrophobic payloads), and scale requirements. Submit your molecular specifications for timeline modeling.
5. Q: Do you provide conjugate design expertise?
A: Our bioconjugation specialists collaborate on structural optimization, including pharmacophore selection, spacer chemistry, and site-specific orientation parameters. Contact us to initiate a collaborative discussion.
How to Contact Us?
Creative Biolabs is dedicated to providing you with the best service and customer support imaginable! Got questions? Project needs? We're all ears and ready to craft a perfectly customized solution just for you! Contact us today and let's bring your ideas to life!
Reference
- Tran, Phuc, et al. "Delivery of oligonucleotides: efficiency with lipid conjugation and clinical outcome." Pharmaceutics 14.2 (2022): 342. Under open access license CC BY 4.0, without modification.