Custom LNP Formulation Service for Circular RNA (circRNA)
Introduction
Nucleic acid therapies face challenges like poor stability, delivery issues, low cellular uptake, and limited in vivo half-life, hindering research. Creative Biolabs' Custom LNP Formulation Service for Circular RNAs accelerates therapeutic development via an advanced LNP platform and tailored approach, offering end-to-end solutions. It provides custom LNP systems, QC reports, and biological validation data to advance research.
Custom LNP Formulation Service for Circular RNAs
The third drug revolution, driven by nucleic acid therapies, is advancing disease treatment. CircRNAs stand out here—their closed-loop structure gives them better stability and longer protein expression duration than linear mRNA, yet their targeted delivery remains a hurdle. LNPs, as multi-component non-viral systems, enable safe RNA transport, and we specialize in optimizing their components for specific circRNAs.
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Introduction to LNP
Lipid nanoparticles are versatile drug delivery vehicles with diameters typically ranging from 50 to 150 nm. They are self-assembling systems that form when a mixture of lipids and an aqueous solution of nucleic acids is mixed under controlled conditions, most commonly through microfluidic mixing.
Fig.1 Lipid nanoparticles (LNP) are mainly composed of ionizable cationic lipids (ICL), helper lipids, cholesterol and its derivatives, and PEG-lipids.1
Types of LNP
While the core components are standard, the specific lipids used can be varied to achieve different delivery profiles. For instance, some ionizable lipids are designed for better endosomal escape, while different PEG-lipids can modulate circulation time and biodistribution. The customization of these components allows for the development of LNPs tailored to specific therapeutic needs.
Encapsulation and Delivery Methods
Fig.2 LNP was synthesized by solvent emulsification.Distributed under CC BY-SA 4.0, from Wiki, without modification.
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Traditional Bulk Mixing Methods
Main types: Include thin-film hydration, solvent diffusion, pore extrusion, sonication, melt emulsification, solvent injection, and bulk nanoprecipitation. -
Microfluidic Technology
Core advantages: More stable and reproducible; offers precise adjustability, short mixing time, low sample consumption, monodisperse particle size distribution, good reproducibility, and scalable production; achieves high controllability in key aspects such as TFR, FRR, mixing conditions, and scalability.- T-junction: A basic device that combines aqueous media with lipid organic solvents (ethanol) under high TFR for rapid mixing, enabling self-assembly of supersaturated lipids into LNPs.
- HFF: Blends lipid organic solutions with aqueous solutions in microfluidic channels, enabling precise regulation of LNP size and EE.
- SHM: Triggers chaotic mixing, where LNP size and shape are controlled by adjusting TFR and FRR.
- Dual-bifurcation circular mixer: Enables large-scale production of uniform LNPs.
- Baffle mixer: Introduces continuous turns for rapid mixing, facilitating fine adjustment of LNP size.
- Tesla mixer: Effectively achieves chaotic mixing, allowing production of smaller NPs over a wider flow rate range.
Detection Indicators
- Particle Size: Measured using Dynamic Light Scattering (DLS), typically expressed as the mean diameter.
- Zeta Potential (ZP): A measure of the particle's surface charge, which influences stability and interaction with biological membranes.
- Polydispersity Index (PDI): A metric for the uniformity of particle size. A smaller PDI denotes a more homogeneous and reproducible batch.
- Encapsulation Efficiency (EE): The percentage of the RNA payload that is successfully encapsulated within the LNPs.
Workflow
Required Starting Materials:
- CircRNA Sequence Information: The full sequence of your circular RNA.
- Desired Expression Target: Details on the target protein or gene of interest for expression.
- Target Cell Line or Organ: The specific cell type or tissue where delivery is intended.
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Project Consultation & Design
Experts consult to understand project goals and circRNA properties, then design a custom LNP formulation strategy. -
CircRNA Synthesis & Pre-formulation QC
Synthesize high-quality circRNA and conduct rigorous QC (integrity checks, concentration verification). -
LNP Formulation & Encapsulation
Use proprietary microfluidic mixing technology to combine lipids and circRNA, forming uniform, monodisperse LNPs with high encapsulation efficiency. -
LNP Characterization & Optimization
Perform analytical tests (particle size, zeta potential, PDI) to ensure LNP stability and effectiveness. -
In Vitro & In Vivo Validation
Validate biological activity via in vitro transfection efficiency assays and in vivo biodistribution studies (if needed) to confirm delivery and expression.
Final Deliverables:
- Ready-to-Use LNP-CircRNA Complex: The final formulated product, ready for your research.
- Comprehensive QC Report: A detailed report including data on particle size (DLS), zeta potential, PDI, and encapsulation efficiency.
- Biological Activity Report: Data from in vitro or in vivo validation studies confirming the function of your therapeutic payload.
Estimated Timeframe: The typical timeframe for this service ranges from 8 to 12 weeks, depending on the complexity of the circRNA construct and the scope of the required validation studies.
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What We Can Offer
At Creative Biolabs, we understand that every research project is unique. Our Custom LNP Formulation Service for Circular RNAs is built around a flexible, consultative approach that puts your specific needs first. We don't just provide a product; we provide a partnership, offering tailored solutions to address your most pressing delivery challenges.
Customized Formulation Development
We provide a comprehensive service for the preparation of specialized LNPs for your specific circular RNA payload.
Precision Manufacturing
Our microfluidic mixing platform ensures precise control over LNP size, uniformity, and encapsulation efficiency.
Tailored Solutions for Your Research
We can provide a variety of LNP formulations and lipid compositions to optimize for your specific cell lines or in vivo models.
Rigorous Quality Control
Our well-established quality system ensures that every batch of LNPs is rigorously characterized for key parameters like particle size, zeta potential, and encapsulation efficiency.
Advanced Analytical Capabilities
We use advanced analytical techniques to provide detailed reports and data, allowing you to move forward with confidence.
Expert Consultation
Our team of experienced scientists is available to consult on every step of your project, from initial design to final validation.
GMP-Certified Production
We adhere to strict quality standards to ensure our products are suitable for advanced applications.
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Customer Reviews
FAQs
Why should I choose circRNA over linear mRNA for my therapeutic project?
Linear mRNA is effective, but its short half-life can limit the duration of its therapeutic effect. The circular structure of circRNAs makes them inherently resistant to degradation, potentially leading to more durable protein expression and a longer-lasting therapeutic effect with a single dose. This is particularly advantageous for protein replacement therapies and long-acting vaccines.
How can I ensure the LNPs will deliver my circRNA to the correct tissue?
While LNPs have a natural tendency to accumulate in the liver, our customization service is designed to mitigate this. We can explore surface functionalization with targeting ligands to direct the LNPs to a specific tissue or cell type beyond the liver. Please feel free to consult with our team to discuss your specific targeting requirements.
What level of encapsulation efficiency can I expect from your service?
We employ optimized protocols and state-of-the-art microfluidic technology that allows us to consistently achieve encapsulation efficiencies greater than 90%. Our rigorous QC process ensures that your valuable payload is fully protected and delivered effectively.
Are your LNPs suitable for both in vitro and in vivo applications?
Yes, our custom formulations are optimized for both in vitro and in vivo use. We offer validation services to test the LNP-circRNA complex in your specified cell lines or animal models, ensuring the formulation is fit for your intended application.
Contact Our Team for More Information and to Discuss Your Project
Reference
- Ramadan, Eslam, Ali Ahmed, and Youssef Wahib Naguib. "Advances in mRNA LNP-based cancer vaccines: mechanisms, formulation aspects, challenges, and future directions." Journal of Personalized Medicine 14.11 (2024): 1092. https://doi.org/10.3390/jpm14111092. Distributed under Open Access license CC BY 4.0, without modification.
