Gene & Drug Delivery - Nanoparticle Characterization
Since 2007 NIS has successfully supported more than 2000 nanoparticle characterization projects for over 200 clients globally. This diverse set of samples have comprised numerous iterations of common delivery vehicles for biologics, nucleic acids and small molecules, including lipid nanoparticles, liposomes, Adeno Associated-Virus (AAV) and other viral vectors. Our extensive cryoEM expertise, quick turnaround and reliable workflows make NIS the company of choice for such studies.
The advantage of cryoEM for gene delivery characterization
Commonly available analytical techniques may require lengthy analysis times and generate averaged information that do not necessarily correlate with observed outcomes. CryoEM, however, provides important structural details on a per-particle basis that cannot be captured by other methods, quickly visualizing individual particles in the size range of 50-500 nm.
The images can be further analyzed to evaluate the particles shape, size and size distribution, morphology, and content. When performed for several batches or preps, this analysis allows for defining correlations between micro- and macro-properties (such as aggregation, solubility, and stability) and can be used as a tool to evaluate the quality of a sample.
Each sample type presents unique challenges and underlying impetus for undertaking cryoEM imaging studies:
AAV and lentiviral vectors
These are the basis for several approved gene delivery therapies. Nevertheless, many challenges remain, including understanding and preventing genotoxicity and immune responses, improving gene transfer or editing, and overcoming manufacturing and regulatory hurdles.
Lipid based nanocarrier systems
Solid lipid nanoparticles, liposomes, polymeric nanoparticles and non-structured lipid carriers are often used as delivery and storage systems to improve biocompatibility and stability, and reduce toxicity of bioactive molecules.
Exosomes have also been proposed as potential drug delivery vehicles. Qualitative and quantitative analysis of these nanoparticles (for example, size, shape, surface modification, load, lamellarity and encapsulation rate) can be very useful, as they may influence biological activity, biodistribution and toxicity and may help further development.
- Bennett, A., Keravala, A., Makal, V., Kurian, J., Belbellaa, B., Aeran, R., Tseng, Y. S., Sousa, D., Spear, J., Gasmi, M., & Agbandje-McKenna, M. (2020). Structure comparison of the chimeric AAV2.7m8 vector with parental AAV2. Journal of Structural Biology, 209(2), 107433. https://doi.org/10.1016/j.jsb.2019.107433
- Rayamajhi, S., Marchitto, J., Nguyen, T. D. T., Marasini, R., Celia, C., & Aryal, S. (2020). pH-responsive cationic liposome for endosomal escape mediated drug delivery. Colloids and Surfaces B: Biointerfaces, 188, 110804. https://doi.org/10.1016/j.colsurfb.2020.110804
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