Cryo-TEM imaging paired with proprietary automated analysis tools delivers reliable, reproducible, per-particle insights into viral and non-viral gene delivery systems. The full/empty/partially full ratio of capsids is one of the most important critical quality attributes (CQAs) to characterize, as the fraction carrying the intended genome versus those that are empty, partially filled, or overfull directly affects the safety, efficacy, and immunogenicity of the product.
Non-Viral Vectors
Lipid Nanoparticles (LNPs) with mRNA, RNA, DNA Payloads
LNPs are increasingly used for gene delivery, however their tendency to be heterogeneous leads to challenges in characterization. Only cryo-TEM provides data on morphology, lamellarity, size distribution, and payload in just one study.
Cryo-TEM imaging can give precise data on:
- Nucleic acid payload distribution in lipid nanoparticles
- Encapsulation efficiency of gene payloads
- Particle morphology, including lamellarity and blebbing
- Particle size distribution
Cryo-TEM is the only technique that can reveal the presence of blebbing in LNP formulations. Direct visualization of individual LNPs along with per-particle analysis reveals the number and approximate size of blebs and whether blebs are empty or loaded.
Our Gene Delivery Experience
We have imaged 220+ AAV samples and solved the 3D structure of AAV to 1.8 Å resolution. Our team regularly presents at the Gene Therapy Analytical Development Summit, discussing how cryo-TEM imaging and quantitative analysis can accelerate development of gene therapy formulations from discovery to the clinic.
