Custom Phosphorodiamidate Morpholino Oligomer (PMO) Synthesis Service
Introduction
Phosphorodiamidate Morpholino Oligomers (PMOs) are neutral-backbone antisense agents for gene expression modulation, critical in treating disorders like Duchenne Muscular Dystrophy. Recent phosphorodiamidate morpholino oligomer synthesis advancements boost production efficiency and enable multi-functional derivatives with better bioavailability.
Creative Biolabs' Custom PMO Synthesis Service uses this advanced phosphorodiamidate morpholino oligomer synthesis platform to deliver high-quality specialized PMOs and novel derivatives. It offers targeted, scalable solutions to advance gene modulation projects from research to preclinical stages, meeting strict standards for cellular and in vivo studies.
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Phosphorodiamidate Morpholino Oligomer Synthesis
This service is centered on providing custom-designed, high-quality PMOs that overcome the limitations of older synthesis techniques, accelerating the path to clinical relevance.
Synthesis Methods
Creative Biolabs utilizes the Phosphoramidite Synthesis Method, which is orthogonal to the traditional P(V) approach. This method allows for synthesis in the 3' to 5' direction, offering crucial compatibility with standard phosphoramidite chemistries used for other backbone types. This P(III) process leads to higher coupling efficiency, resulting in a cleaner final product and enabling the seamless introduction of complex modifications at various positions.
Fig.1 Schematic diagram of the synthetic cycle scheme for preparing PMO using the P(III) chemical method.1
Advantages
The key advantages are rooted in the P(III) technology: Enhanced Purity (HPLC-verified ≥95%), Superior Scale-up Capabilities, and the Ability to Synthesize Chimeric Oligomers by co-synthesizing different backbone chemistries on the same solid support. This flexibility is vital for creating next-generation therapeutic leads.
Application
PMOs are principally applied in Splicing Modulation (e.g., exon skipping for DMD), RNA knockdown, and Targeted Antisense Therapy. Our custom Phosphorodiamidate Morpholino Oligomer Synthesis Services are also heavily utilized in conjugating delivery vehicles for enhanced biodistribution to hard-to-target tissues (e.g., central nervous system, muscle).
Workflow
The Creative Biolabs workflow is designed for maximum clarity, control, and efficiency, making it highly suitable for visualization as a strategic flowchart.
| Stage | Activities Involved |
|---|---|
| Project Initiation & Design Review | Creative Biolabs computational chemists analyze the client's target sequence (exon skipping or splicing correction), desired length, and specified modifications (e.g., cell-penetrating peptides). |
| P(III) Solid-Phase Synthesis | Automated synthesis utilizing advanced P(III) phosphoramidite chemistry for high-efficiency coupling and rapid chain elongation (3' to 5' direction). |
| Cleavage and Deprotection | The synthesized PMO is cleaved from the solid support, and all temporary protecting groups are removed under optimized conditions to maintain backbone integrity. |
| Purification and Quality Control (QA/QC) | High-resolution HPLC (High-Performance Liquid Chromatography) is used for purification to achieve ≥95% purity, followed by rigorous analytical validation. |
| Final Formulation and Delivery | The purified PMO is typically lyophilized (freeze-dried) and packaged according to client specifications, ensuring long-term stability. |
Required Starting Materials
- Target mRNA Sequence Details (including exon/intron junctions for splicing)
- Desired PMO Length and Specific Backbone/Base Modifications
- Targeted Delivery/Conjugation Strategy (e.g., type of CPP or ligand required)
Final Deliverables
- High-Purity Lyophilized PMO Compound (≥95% purity, specified mass/concentration)
- Comprehensive Certificate of Analysis (CoA) with batch specifications
- Full Analytical Data Report (HPLC chromatograms, ESI-Mass Spectrometry for structure verification)
Estimated Timeframe
Typically, 6-10 weeks, depending on PMO sequence length/complexity and commercial availability of specialized conjugation building blocks
What We Can Offer: Unlocking PMO Design Flexibility
Creative Biolabs provides biology experts with precise, scalable PMO synthesis solutions, supported by superior chemistry and strict quality control. Our offerings are designed to handle next-generation antisense therapeutic complexity, ensuring top standards from research concept to pre-clinical delivery.
Expert Custom Conjugation and Targeting
Offer specialized synthesis of PMO derivatives with customized delivery systems (CPPs, GalNAc ligands, lipid moieties) to enhance biodistribution to tissues like the CNS and muscle.
Seamless Scale-Up for IND Readiness
Provide reliable large-scale manufacturing, transitioning from research-grade milligrams to gram-scale for IND-enabling GLP studies while maintaining quality.
Custom Chimeric and Modified Backbones
Deliver bespoke chimeric oligonucleotides by integrating PMO backbone with other modifications (PNA, 2'−O-methyl RNA) for exploring RNA splicing and boosting stability.
End-to-End Analytical Quality Assurance (QA/QC)
Include comprehensive QC data (High-Resolution HPLC, ESI-Mass Spectrometry) to confirm identity and purity, ensuring chemical integrity for sensitive experiments.
Collaborative Design and Optimization
Computational chemists collaborate to review target sequences and optimize synthesis strategies for non-standard lengths, complex modifications, and challenging sequences, maximizing efficiency and therapeutic potential.
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Customer Reviews
FAQs
Q: What is the main difference between your PMOs and those synthesized via traditional methods?
A: Our PMOs are synthesized using a modern P(III) phosphoramidite method, which offers significantly higher coupling efficiency and purity than the older P(V) chemistry. This allows us to produce cleaner product batches faster and at a larger scale, which is essential for consistent in vivo study results.
Q: How do PMOs compare to other antisense oligonucleotides (AONs) like PS-DNA?
A: PMOs are distinct because they have a neutral backbone, which provides high nuclease resistance and minimal toxicity, making them highly desirable for certain gene therapy applications like exon skipping. We are happy to review your specific therapeutic goal and compare PMO efficacy against alternatives for your target.
Q: What is the minimum purity I can expect for my final product?
A: For preclinical and in vivo applications, we guarantee a minimum purity of ≥95% for our PMOs, as verified by analytical HPLC and Mass Spec. We understand that low purity can introduce artifacts, and our stringent QC process is designed to deliver reliable therapeutic agents.
Q: What information do I need to provide to get an accurate quote and timeline?
A: To provide a precise quote, we require your full PMO sequence, the desired synthesis scale (mg to g), and details of any required backbone modifications or conjugates. Providing these details upfront significantly shortens the design phase.
Creative Biolabs' Custom Phosphorodiamidate Morpholino Oligomer Synthesis Service provides a powerful, high-resolution solution for therapeutic development. Creative Biolabs delivers high-purity, scalable PMOs and complex conjugates—key to de-risking and accelerating your path to clinical validation. We are your trusted partner in unlocking the full potential of antisense technology.
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Reference
- Paul, Sibasish, and Marvin H. Caruthers. "Synthesis of backbone-modified morpholino oligonucleotides using phosphoramidite chemistry." Molecules 28.14 (2023): 5380. https://doi.org/10.3390/molecules28145380. Distributed under Open Access license CC BY 4.0, without modification.
