Characterization of Nucleic Acid Drug Products
As nucleic acid therapeutics rapidly evolve; your development program may require innovative strategies tailored to these specialized products. Our experience spans various types of nucleic acid-based drug products, including high-concentration oligonucleotide formulations, lipid nanoparticles (LNP), virus-like particles (VLP), viruses, and other nanoparticle formulations.
Within this dynamic landscape, gaining a deeper understanding of your therapeutic’s safety, effectiveness, and development potential is crucial. Analytical and biophysical drug product characterization provides insight into your drug product to support analytical, formulation, and process development. Our commitment extends beyond routine identity, purity, assay, and safety testing; we offer customized services and advanced characterization studies to meet your unique needs.
Dynamic Light Scattering (DLS) is the most common method for determining LNP sizes and, in an electric field, the zeta potential of particles. We also use Nanoparticle Tracking Analysis (NTA) to determine the size distribution of nanoparticles. Less commonly used is Size Exclusion Chromatography with Multiple Angle Light Scattering (SEC-MALS) to determine both the size distribution and the absolute molecular mass of LNPs.
The quantity of nucleic acids entering the LNP manufacturing process is readily controlled, but the resulting LNPs contain a mixture of nucleic acids free of lipids partially encapsulated or bound to the LNP surface, and those that are fully encapsulated. We provide guidance and support based on our experience with multiple orthogonal approaches, including dye-based approaches (e.g. ribogreen) to characterize encapsulation efficiency of the nucleic acid packaging into lipid particles.
It is important to control the ratio of each type of lipid in the nanoparticle. Our team routinely develops and uses chromatographic methods (e.g., HPLC, U(H)PLC with ELSD, CAD, or MS detectors) to determine the lipid composition in your LNPs sample. We also use tools such as LC-MS to characterize lipid degradation products, such as cholesterol oxidation.
Viruses & Virus-like Particles
Capsid Protein Characterization
Our experts use multiple approaches to determine the protein composition in the particle capsid (e.g., H(U)PLC, capillary electrophoresis, LC-MS). We also characterize post-translational modifications to support manufacturing and identify any impurities observed in stability studies.
While DLS can determine capsid size, we also offer SEC-MALS and asymmetric field flow fractionation (AF4) with MALS to characterize the size and composition of viral particles. These approaches are orthogonal to analytical ultracentrifugation (AUC) and microscopy (e.g., cryoTEM).
Integrated Laboratory Services
Characterization insights apply across the development timeline, and our experts are ready to sync with your project. Discover additional opportunities for us to partner with you.