Exosome Manufacturing Services
Compared with other vehicles, exosomes as an RNA carrier have prodigious features, including appropriate pharmacokinetic (PK), excellent permeation into physiological barriers, and tolerable immunological responses. To meet global customers' needs for effective and safe delivery of therapeutic mRNA, Creative Biogene is proud to offer exosome manufacturing services. With years of experience and expertise in exosome technologies, we are good at exosome process development and optimization as well as large-scale manufacturing.
Fig 1. Schematic representation of cellular nanoporation (CNP) generated EVs for targeted nucleic acid delivery. (Yang, Z., et al, 2020)
The main sources of exosomes
To develop exosomes as drug delivery systems, one of the most crucial steps is to effectively isolate them from a wide spectrum of different sources without cellular and molecular contaminations. Here, we list several important sources of exosomes.
- Human embryonic kidney cell-derived exosomes
The human embryonic kidney (HEK) cell line (HEK293T) has been applied in a broad range of investigations as an extracellular vesicle (EV) donor, because of their easy growth, capacity for high yield of EVs, and high transfection efficiency. The studies demonstrated that 293 T cell-derived exosomes have common features with the different tissues, which improve their membrane fusion in these tissues. Besides, the desirable characteristics of HEK Expi293F cells, such as the minimal toxicity and immunogenicity, make them promising exosome producers for clinical use.
- Bone marrow stem cell-derived exosomes
Bone marrow stem cells (BMSCs) have been proposed as clinical-grade exosome producers for cellular therapy. Repeated administration of engineered exosomes (BMSC-derived iExosomes) had been reported to induce no detectable toxic or deleterious immune responses in mice.
- Immature dendritic cell-derived exosomes
It is believed that exosomes are attractive and ideal drug delivery vectors for tumor-targeted therapy. Researchers found that immature dendritic cell (imDC) -derived exosomes enable weak stimulation of naïve T cells and siRNA delivered by imDCs-derived exosomes in vivo did not elicit adverse immune responses or any toxic reactions.
- Milk-derived exosomes
Due to their safety, easy scalability, and biocompatibility, milk has been proposed as a good alternative source of exosomes. A study had shown that short-term (1-6 hours) and long-term (15 days) administration of milk-derived exosomes to animals didn’t induce any toxicity or adverse immune response. Therefore, they are potential carriers for the delivery of chemotherapeutic drugs.
- Red blood cell-derived exosomes
As the most abundant cell type (accounting for 84%) in the body, red blood cells (RBCs) are a promising cell origin for producing exosomes. The RBC-derived exosomes can be easily obtained from multiple different sources, such as from the patients’ blood or from the blood banks. Currently, the RBC-derived exosomes have been used for drug delivery in certain situations.
Service offering in Creative Biogene
We provide one-stop exosome large-scale manufacturing services. Our standardized manufacturing process is strictly in accordance with good manufacturing practice (GMP), involving the specific cell types, optimal cultivation conditions, such as dissociation enzyme, culture medium, and cultivation system. We can work with you to develop the following manufacturing stages,
- Cell cultivation
The choice of specific cell types and cultivation conditions is critical.
The process includes three steps; cell debris filtration, concentrating condition medium, and separation from the concentrated condition medium.
- Quality control (QC)
To ensure the quality and quantity of the final products, the harvested exosomes will be characterized by different techniques, such as nanoparticle tracking analysis (NTA), imaging flow cytometry, transmission electron microscopy (TEM), tunable resistive pulse sensing (TRPS), and mass spectrometry (MS).
- Generation of exosome QC reports
The comprehensive report includes exosome quantity, zeta-potential, size distribution, RNA/protein quality, and so on.
The workflow of our services
If you are interested in our services, please feel free to contact us. We will reply to your message shortly.
- Yang, Z., et al. (2020). "Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation." Nature biomedical engineering, 4(1), 69-83.
- Aslan, C.,et al. (2021). "Exosomes for mRNA delivery: a novel biotherapeutic strategy with hurdles and hope." BMC biotechnology, 21(1), 1-12.