LNP-Therapeutic Oligonucleotide Delivery Service
Lipid nanoparticles (LNPs) have emerged as the gold standard delivery vehicle, providing a robust and versatile solution for shielding fragile nucleic acids from nuclease degradation and facilitating efficient intracellular uptake. At CD BioGlyco, we specialize in the precision engineering of LNP-based delivery systems designed specifically for therapeutic oligonucleotides, including small interfering RNA (siRNA), antisense oligonucleotides (ASOs), and microRNA (miRNA). By optimizing the spatial arrangement and chemical composition of lipids, CD BioGlyco enables the delivery of genetic payloads that were previously considered "undruggable." Our services bridge the gap between discovery and clinical application, providing researchers with the specialized tools needed to achieve high potency and minimal off-target toxicity.
Key Technologies
- Microfluidic Mixing Technology: We utilize high-precision microfluidic mixing platforms that allow for the controlled nanoprecipitation of lipids and oligonucleotides. By precisely managing flow rates and ratios, we produce LNPs with highly uniform size distributions and a low polydispersity index (PDI).
- Targeted Ligand Conjugation: To move beyond liver-centric delivery, we employ advanced conjugation technologies, such as GalNAc-L96 and custom peptide ligands. These modifications allow for active targeting of specific cell types, enhancing the therapeutic index and reducing the required dosage.
Advanced LNP-Therapeutic Oligonucleotide Delivery Service
As a core component of our Therapeutic Nucleic Acid Development Platform, CD BioGlyco provides a comprehensive therapeutic oligonucleotide delivery service. We recognize that every oligonucleotide sequence has unique physicochemical properties and therapeutic goals. Our service scope is designed to accommodate a wide variety of payloads and delivery requirements:
- Custom LNP Formulation Development: We offer tailored formulation services where we optimize the molar ratios of ionizable lipids, phospholipids, cholesterol, and PEGylated lipids to suit your specific siRNA, ASO, or miRNA payload.
- Oligonucleotide Encapsulation: Our platform supports high-efficiency encapsulation of various nucleic acid sub-substances. Whether you are working with single-stranded ASOs or double-stranded siRNAs, we ensure maximum loading and stability.
- Organ-Specific Delivery Solutions: While LNPs naturally accumulate in the liver, we provide specialized modification services to redirect LNPs to the lungs, spleen, or immune cells, expanding the reach of your therapeutic candidates.
- Stability and Analytics: Every delivery vehicle undergoes rigorous testing to ensure it meets the highest standards of stability and purity, ready for immediate use in in vitro or in vivo studies.
Workflow
Project Consultation and Design
Our experts collaborate with you to define the target profile, payload characteristics, and desired biodistribution. We select the most appropriate lipid components and targeting ligands from our extensive library to begin the design phase.
Payload Synthesis and Preparation
We ensure the therapeutic oligonucleotide is synthesized to the highest purity standards. If provided by the client, the payload undergoes a preliminary quality check to confirm integrity and concentration before formulation begins.
High-Precision Formulation Mixing
Utilizing advanced microfluidic systems, we combine the organic lipid phase with the aqueous oligonucleotide phase. This process is carefully controlled to achieve the desired particle size, ensuring optimal cellular uptake.
Purification and Buffer Exchange
The crude LNP mixture is purified using tangential flow filtration (TFF) or dialysis to remove organic solvents and unencapsulated material. The LNPs are then transitioned into a physiologically compatible buffer for maximum stability.
Comprehensive Physicochemical Characterization
We perform a battery of tests to confirm the quality of the LNPs, including dynamic light scattering (DLS) for size and PDI, and Ribogreen assays to calculate the encapsulation efficiency.
In Vitro and In Vivo Validation
We conduct cellular uptake assays and biodistribution studies to confirm that the LNP-oligonucleotide complex reaches its target and achieves the desired gene silencing or modulation effect.
Publication Data
DoI: 10.3390/pharmaceutics13040544
Journal: Pharmaceutics
IF: 5.5
Published: 2021
Results: This study explores the optimal lipid composition of LNPs containing self-degradable ssPalmO-Phe for delivering siRNA and ASOs. The optimal LNP composition differs between siRNA (ssPalmO-Phe/Chol = 70/30 with 1.5% DMG-PEG2000) and ASO (ssPalmO-Phe/DOPC/Chol = 40/20/40 with 1.5% DMG-PEG2000), and both differ from that for mRNA. Key factors include extracellular stability for mRNA, endosomal escape for siRNA, and cellular uptake for ASOs. LNPs significantly enhance knockdown efficiency (e.g., 146-fold for ASOap), but ASO encapsulation may increase hepatotoxicity at lower doses. Empty LNPs show no toxicity, confirming safety of the delivery system. The findings highlight the need to optimize LNP composition based on nucleic acid type for effective oligonucleotide delivery.
Fig.1 ssPalmO-Phe for the oligonucleotide delivery. (Tanaka, et al., 2021)
Applications
Oncology Therapy Research:
LNPs are used to deliver siRNA or miRNA that silence oncogenes or restore tumor-suppressor functions. Our service enables targeted delivery to tumor tissues, enhancing the efficacy of cancer immunotherapies.
Rare Genetic Disorders
We support the development of therapies for conditions like spinal muscular atrophy (SMA). Our ASO-LNP formulations facilitate splice-switching and protein restoration in hard-to-reach tissues.
Infectious Disease Vaccines
Beyond mRNA, oligonucleotides serve as powerful adjuvants. Our LNP delivery systems optimize the immune response by ensuring these molecules are effectively internalized by antigen-presenting cells.
Metabolic and Liver Diseases
Utilizing our specialized GalNAc-L96 targeting technology, we provide highly efficient delivery to hepatocytes. This is ideal for treating chronic conditions like hypercholesterolemia or transthyretin amyloidosis through RNA interference.
Advantages
Superior Particle Monodispersity
Our microfluidic-based production ensures a PDI typically below 0.1, resulting in a homogeneous product that provides consistent pharmacokinetic profiles across different batches and experimental subjects.
Scalability from Lab to Pilot
Whether you need small-scale batches for initial in vitro screening or larger quantities for animal studies, our processes are designed to maintain consistency throughout the scale-up phase.
Reduced Immunogenicity and Toxicity
By utilizing pH-sensitive lipids and high-purity PEGylated lipids, our LNPs exhibit a favorable safety profile with minimal systemic inflammation, allowing for higher dosing and repeated administration if necessary.
Expert Technical Support
Clients work directly with PhD-level scientists. We provide not just the delivery vehicle, but the deep biological expertise required to troubleshoot complex delivery challenges and interpret experimental data.
Frequently Asked Questions
Customer Review
"Their custom LNP formulation achieved much higher gene silencing efficiency in our primary cell models than any of the commercial reagents we previously tested. The characterization data were thorough and gave us great confidence for our upcoming in vivo trials."
– D.R., Medical Center
"CD BioGlyco's LNP delivery service not only protected our molecules but also improved the biodistribution profile significantly. Their expertise in lipid chemistry is truly world-class."
– E.S., Innovative Biotech Startup
"Working with CD BioGlyco was a seamless experience. The communication was proactive, and the quality of the LNPs delivered was top-tier. Their microfluidic approach ensures the kind of batch-to-batch consistency."
– D.T., Pharmaceutical Company
Associated Services
CD BioGlyco is committed to providing researchers with the most advanced LNP-therapeutic oligonucleotide delivery services available. By combining innovative lipid chemistry, precision microfluidics, and deep biological insight, we empower our clients to overcome delivery hurdles and accelerate the development of life-changing genetic therapies. Please feel free to contact us to provide a customized solution for your delivery needs.
Reference
- Tanaka, H.; et al. Delivery of oligonucleotides using a self-degradable lipid-like material. Pharmaceutics. 2021, 13(4): 544. (Open Access)