Design of Gene & Drug Delivery Systems Service | Cryo-EM
- Structural Analysis: Visualizing the size, shape, lamellarity, and encapsulated content distribution of drug delivery systems.
- Heterogeneity Assessment: Detecting population diversity, aggregation states, and morphological defects.
- Surface Interaction Studies: Observing ligand presentation and surface roughness.
- Payload Encapsulation Monitoring: Differentiating loaded versus unloaded carriers and evaluating internal organization.
The development of efficient gene and drug delivery systems is fundamental to modern therapeutics, offering pathways for targeted treatment, improved bioavailability, and reduced systemic toxicity. Success in this area requires not only innovative carrier designs but also precise structural characterization at the nanoscale to ensure delivery efficiency, stability, and biocompatibility. Cryogenic electron microscopy (Cryo-EM) has emerged as a pivotal technology for visualizing the ultrastructure of nanoparticles, liposomes, niosomes, polymeric systems, viral vectors, and other delivery platforms in their native, hydrated states. Cryo-EM offers near-atomic resolution, making it uniquely suited for studying fragile and dynamic delivery vehicles.
Figure 1. Drug Delivery Systems for the Diagnosis and/or Therapy of Various Diseases
MtoZ Biolabs offers a comprehensive Design of Gene & Drug Delivery Systems Service based on Cryo-EM, supporting researchers and developers from early formulation design to in-depth structural validation. Our Design of Gene & Drug Delivery Systems Service bridges formulation development and structural visualization, enabling the optimization of delivery systems based on high-resolution, data-driven insights.
Cryo-EM enables direct imaging of nanoparticles and carrier systems embedded in vitrified ice, preserving their morphology, surface features, and internal architecture. This provides unparalleled advantages in:
These insights are critical for rational design, quality control, and regulatory submission of gene and drug delivery products.
Analysis Workflow
1. Consultation and Project Planning
We discuss delivery platform types (e.g., LNPs, liposomes, exosomes, viral vectors), therapeutic payloads (e.g., mRNA, siRNA, proteins, small molecules), and project objectives.
2. Formulation Design and Optimization
Based on client needs, we assist in selecting or formulating appropriate carrier systems with consideration for stability, encapsulation efficiency, and biological targeting.
3. Cryo-EM Grid Preparation
Samples are vitrified using optimized protocols to capture native particle structures without artifacts.
4. Cryo-EM Imaging and Data Acquisition
High-resolution imaging is performed using state-of-the-art Cryo-TEM equipped with direct electron detectors under low-dose conditions.
5. Structural Analysis and Interpretation
Comprehensive analysis includes size distribution, morphology, lamellarity, payload distribution, aggregation analysis, and statistical population characterization.
6. Reporting and Recommendations
Clients receive comprehensive reports with representative micrographs, qualitative and quantitative analysis, and other detailed information. We also provide actionable recommendations for formulation improvement or validation.
Service Advantages
☑️Native Structure Preservation: Our optimized vitrification and imaging workflows preserve the native structure of lipid-based, polymeric, and vesicular carriers.
☑️Data-Driven Delivery Optimization: Based on detailed particle analysis, we provide actionable suggestions to improve encapsulation efficiency, stability, and batch consistency.
☑️Support Across Development Stages: Whether in early screening or late-stage validation, our service adapts to research or preclinical needs, accelerating delivery system development.
☑️Broad Expertise in Nanocarriers: Our multidisciplinary team ensures tailored solutions for a wide variety of therapeutics, from nucleic acids to proteins and small molecules.
☑️High-Resolution Results: Using advanced Cryo-EM platforms, we deliver consistent, reproducible structural data to support robust decision-making in drug development.
Applications
1. Non-Viral Nanoparticle Delivery Systems
Our service supports the design and structural validation of LNPs and polymeric carriers for gene therapy and vaccine delivery. We enable optimization of nanocarriers by visualizing encapsulation efficiency, particle morphology, and homogeneity via Cryo-EM.
2. Small Molecule Nanoformulations
Our service characterizes liposomes, micelles, and hybrid systems designed to enhance small molecule solubility and bioavailability.
3. Viral Vector-Based Gene Delivery
We assist in assessing viral capsid integrity, genome packaging, and surface modification uniformity critical for gene transfer efficiency.
4. Exosome and Extracellular Vesicle Platforms
Through Cryo-EM imaging, we help optimize natural or engineered vesicle systems for targeted drug and gene delivery applications.
Case Study
Cryo-EM Structural Analysis of the AAVv128 Gene Delivery System
Recombinant adeno-associated viruses (rAAVs) have proven effective as gene therapy vectors, but high-dose administration poses safety challenges. A novel AAV capsid variant, AAVv128, was engineered to enhance transduction efficiency in retinal tissues following intraocular delivery. Using Cryo-EM at 2.1 Å resolution, researchers revealed structural adaptations in AAVv128 critical for improved receptor binding, nuclear uptake, and endosomal escape. This structural insight correlated with enhanced therapeutic outcomes, including complete suppression of severe CNV lesions in a non-human primate model. This study highlights how Cryo-EM-based structural analysis plays a pivotal role in the rational design and optimization of next-generation viral gene delivery systems.
Figure 2. Cryo-EM Reveals Differences between AAVv128 and AAV8
FAQ
Q1: What types of delivery systems can you support?
A1: We support a wide range of delivery platforms, including lipid nanoparticles (LNPs), polymeric carriers, viral vectors, liposomes, micelles, exosomes, and hybrid systems for gene and drug delivery. If you have other specific delivery systems or customized requirements, please feel free to contact us for further consultation.
Q2: How does Cryo-EM contribute to delivery system optimization?
A2: Cryo-EM enables direct visualization of nanoparticle morphology, encapsulation efficiency, structural integrity, and heterogeneity, providing critical data to guide formulation improvements.
Q3: What services do you provide for the design of gene and drug delivery systems?
We provide comprehensive services including formulation consultation, Cryo-EM sample preparation, high-resolution imaging, particle size distribution analysis, morphological assessment, encapsulation efficiency evaluation, and structural optimization recommendations. In addition, we offer customized analysis based on specific project needs, such as aggregation profiling, internal payload distribution studies, or comparative structural assessments across different formulations.
MtoZ Biolabs is committed to accelerating the rational design and optimization of gene and drug delivery systems through state-of-the-art cryo-EM technologies. To learn more about our Design of Gene & Drug Delivery Systems Service integrated with Cryo-EM, or to discuss your project needs, please contact us.
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