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Exosomes have been identified to have a plethora of functions but their ability to work as an extracellular vehicle is from far one of the most interesting ones.

With a lot of projects in early stages, exosome development is facing various challenges to bring those projects dive into clinical phase manufacturing.

At Naobios, we address these challenges by drawing on a solid base of expertise built on a 20-year experience as a GMP pharmaceutical establishment, producing Challenge agents, Oncolytic viruses, Viral vaccines and Viral vectors. Our goal is to bring our customers’ projects into clinical phase manufacturing with a robust process.

The exosome is a protein complex capable of degrading different types of RNA molecules. It is found in both eukaryotic and archaeal cells, while bacteria have another complex that handles similar functions. Exosomes are 30-150 nm vesicles, which are discharged by a cell into its environment. They can be formed by any cell type, including lymphocytes, platelets, mast cells, dendritic cells, stem cells, astrocytes or tumor cells.

As extracellular vesicles, exosomes can deliver proteins, lipids and nucleic acids to recipient cells as they circulate in the extracellular space. Exosomes are therefore mediators and play an important role in intercellular communication. They also play a role in immune response, neurodegenerative diseases and tumor progression.

Extracellular vesicles (EVs) originating from eukaryotic and prokaryotic cells are playing a crucial role in intercellular communications. We can find them in the cells and tissues environment and contribute to different biological media such as biofluids. They are a cluster of nano-sized vesicles with different sizes that can be secreted into the extracellular environment.

These vesicles are essential to the normal functioning of the Golgi apparatus as they move lipids and proteins between different parts of it. They provide energy for chemical reactions and work as intercellular immune mediators, participating in cell-to-cell communication and delivering information between cells, modulating their physiological condition.

Extracellular vesicles are isolated from body fluids, cell growth medium or serum and have several varieties of closed membrane vesicles. These vesicles are classed down under specific size, shape, composition and biogenesis process. We can find four subclasses of extracellular vesicles:

These vesicles are small cellular containers that are used for a large variety of functions such as moving molecules, digesting materials, secreting substances, or regulating the pressure in the cell.

This places extracellular vesicles at the heart of research for their potential use as vectors for the targeted delivery of drugs and biologics to specific cells. As mediators, exosomes play a key role in intercellular communication and can therefore serve as powerful therapeutic vectors.

As a field in development, the exosomes manufacturing uses techniques that are not yet optimized. The isolation and purification of exosomes remains difficult as there are components such as lipoproteins or other extracellular vesicles with a size close to exosome’s size.

Exosome manufacturing relies on the ability to produce a large number of cells and scaling up needs to be adapted to maximize the surface area. Limiting cell death is necessary to avoid any impurities from apoptotic blebs as some can overlap exosome sizes and increase the heterogeneity of the solution.

For downstream process (DSP) two main methods can be used such as size exclusion using ultracentrifugation, the most common method or sedimentation to separate exosomes from other vesicles. Ultracentrifugation has been commonly used to purify vaccines but we have seen a usage reduction of this method due to the rise of other methods such as chromatographic separation and filtration.

The characterization step is also a real challenge with heterogeneous isolates that lead to a mixed size distribution with difficulties to establish vesicle contents.

Regarding these issues there are still some questions in terms of cost, safety and reproducibility for exosome bioproduction. With projects that are in pre-clinical or early clinical stages, exosome manufacturers are working to show the potential of exosome-based therapies in clinical stages. For exosomes to be used in clinics, guidelines still need to be defined regarding biopharmaceutical regulations.

Exosome manufacturing is experiencing an emerging rise as a novel therapeutic platform and even if few clinical studies have been performed so far and no standard process is defined, these extracellular vesicles are progressing towards clinic manufacturing.

At Naobios with our state-of-the-art services we can make your exosome projects happen. Relying on a strong CDMO expertise with a 20-year experience as a GMP pharmaceutical establishment, producing Challenge agents, Oncolytic viruses, Viral vaccines and Viral vectors, we are uniquely suited for the manufacturing of exosomes compared to other new CDMO on the market solely dedicated to exosome market.

We are a GMP-certified Pharmaceutical Establishment by the French Regulatory Agency ANSM, we have BSL2 and BSL3 manufacturing suites and we have an extensive track record in Process Development, cell culture manufacturing, USP and DSP. We have already manufactured more than 55 GMP batches of Drug Substances for Clinical phase studies. We are working with US-based companies like Flugen, and Asia-based companies like Sumagen and others.

We can provide aseptic manufacturing (DS and DP) in compliance with the new Annex I GMP regulations. Naobios can also perform the full range of analytical testing in-house required for exosomes, offering an end-to-end solution to go fast to clinics.

Working regularly on complex processes (USP and DSP), we have the capacity to define the good process and to optimize it. Following the project flow, we will then be able to manufacture GMP clinical batches for clinical study managing characterization and quality control.

There is a wide range of Clinical applications for exosomes. First, they can be used as drug delivery carriers in cancer therapy to deliver therapeutic molecules in tumor cells.

They can also be useful as biomarkers in the diagnostic field, allowing to diagnose various diseases. Finally they can be used as vectors for gene delivery in the gene therapy field or even in regenerative medicine as they can enhance tissue repair and regeneration.

Exosomes have emerged as an innovative and promising field, counting on early-stage projects transferring into clinical manufacturing. They have the ability to be used as biomarkers and act as therapeutic vectors. They are now recognized as having profound effects on both physiological and pathological processes.

Some challenges still need to be overcome and at Naobios we are addressing these challenges in the best possible way to bring your project fast into clinical manufacturing.