Virus & Virus-Like Particles

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Cryo-TEM is a powerful analytical tool for any viral vector-based or virus-like particle (VLP) gene therapy or vaccine in all phases of the drug and vaccine development process.

Viral vectors, including prominent ones such as vesicular stomatitis virus (VSV), Newcastle disease virus (NDV), influenza virus (IFV), adenovirus (AdV), and poxvirus, can be used for gene replacement, as well as their genomes can be modified to contain one or more foreign genes encoding the targeted antigens of interest, which in turn induces a robust humoral and cellular immunity against human diseases. This approach has gained significant attention in recent years, especially with the development of COVID-19 vaccines like those from AstraZeneca and Janssen, both AdVs. 

Virus-like particles (VLPs) have gained significant attention and recognition as promising tools for therapeutics delivery as well as vaccine development because of their unique properties and advantages due to their structural stability, high payload capacity, and versatile surface modification potential. VLPs offer a versatile platform for delivering genes and drugs, facilitating targeted and efficient therapies with enhanced safety profiles.

Cryo-TEM is an excellent orthogonal technique that complements and improves data obtained using DLS, AUC, or SEC and is important for establishing the historical comparability and therapeutic and clinical equivalence of the product for FDA filings.

Visualizing viral vector formulations on a per-particle basis, from cryo-TEM images to 3D structure determination.

Whether your formulation is a VLP or an icosahedral, enveloped, or non-enveloped viral particle, we offer multiple imaging & analysis services to better understand your virus-based formulation beyond purely visualizing the particles.

Particle classification analysis can be used to categorize and quantify morphological features in and between formulations in order to help researchers better understand the efficacy, safety, and immunogenicity of their formulation. 

To optimize virus-based vaccine design, cryo-TEM or negative stain TEM images can be used for example to quantify the fraction of non-intact versus intact virus particles in a sample, or the number of full, empty, and partially filled capsids, or help evaluate antigen distribution on the particle surface by categorizing particles that are densely decorated, sparsely decorated, or not decorated with surface glycoprotein spikes.

We also offer automated tracing and size distribution analysis of particles in cryo-TEM or negative stain TEM images, a quality attribute important for assessing batch-to-batch variability, formulation and process development, and process validation.

Another analytical tool we provide is 2D class averaging analysis. For viral vectors that are homogeneous in size and shape, cryo-TEM or negative stain TEM images of virus & VLP particles can be aligned and class averaged in order to better understand structural details of the capsid, including domain structures, in 2D. 

For virus & VLP particles that are homogeneous in size and morphology, cryo-TEM images can also be used to determine the full 3D structure at high resolution. A 3D structure can provide information on for example antibody binding sites (epitope mapping), if and how mutations affect the capsid structure, receptor binding sites, and possibly post-translational modifications. 

When obtaining a high resolution 3D reconstruction is challenging due to structural and compositional variation from one viral particle to another, we offer cryo-electron tomography (cryo-ET). In this technique, a low resolution 3D structure is reconstructed from a series of 2D projection images, which can then provide information on for example native states of viruses without intrinsic symmetry (eg retroviruses), or can be used to assess possible interactions between viral vectors and adjuvant, if present.

We can work with viral vectors that require safety level BSL-1 or BSL-2.

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Frequently Asked Questions

cryo-TEM image and 3d structure reconstruction of adenovirus

How many particles do you count, or images do you analyze per sample or grid?

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Can I see an example report for your automated capsid ratio analysis?

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