Extracellular Vesicle Development Service

Development of Extracellular Vesicles for Gene Delivery

Extracellular vesicles (EVs) are cell-derived, naturally phospholipid-coated nanovesicles that have been identified as natural carriers of nucleic acids, generating interest in their use for RNA interference and gene therapy applications. Our company focuses on EVs as vectors for gene therapy and on recent developments in EV engineering to help our customers develop effective EV-based gene therapies, offering the possibility of new precision therapies for rare diseases.

Background

Extracellular vesicles (EVs), including exosomes and microvesicles, play an important role in the transport of biomolecules and nucleic acids (including mRNA) in the body. In recent years, EVs have emerged as potential carriers for nucleic acid therapy due to their inherent biocompatibility, ability to cross physiological barriers, and low immunogenicity. Recent studies have successfully developed electroporation methods for loading siRNAs into EVs leading to powerful gene-silencing effects without toxicity to biological systems. This suggests that EVs are a new generation of gene carriers that can be used to develop safe and effective gene therapies.

Although many challenges need to be overcome before EV-based delivery systems can be used in humans, EVs offer better biocompatibility and side effects than lipid nanoparticles (LNPs) and adeno-associated viruses (AAVs), making them more attractive in gene therapy. They are produced by most cell types and have natural biological advantages, promising applications as non-invasive diagnostic, prognostic, and therapeutic tools for a range of human diseases including rare diseases.

Fig. 1 Active loading of cargo RNA into EVs via targeted and modular EV loading (TAMEL). (Zhao M X, et al., 2016)

Our Services

Our researchers provide our customers with specialist scientific services and solutions to address the challenges of developing EVs as delivery systems for nucleic acids, such as suboptimal nucleic acid drug loading efficiency and quality control issues. Our services include, but are not limited to:

Characterization of EVs
We provide electron microscopy, Western blotting, flow cytometry, and other techniques to help customers characterize the properties of EVs.
EV therapeutic engineering
We offer two ways to load nucleic acids into EVs.
- EV loading methods
  Purified EVs can be used for loading therapeutic drugs in a variety of ways. Generally, we load large nucleic acids into EVs by fusing exosomes with liposomes. This produces hybrids with liposome carrying capacity and the ability for EVs to interact with and enter recipient cells.
- Parental cell-based engineering
  We engineered donor cells to release modified EVs to overcome the low loading efficiency of other methods for some macromolecules. We offer the TAMEL platform for active and specific RNA loading into EVs. And we offer EXOtic, a novel parental cell-based mRNA loading strategy for specific packaging/delivery of RNA.
Improvement of EV gene delivery systems
Our researchers have developed a variety of strategies to help customers engineer natural EVs for better gene therapy results. Our services aim at:
- Increasing EV production
  The low yield of EV secretion is a major obstacle to large-scale production. In order to increase the EV yield, we improved the EV isolation method by applying different external stimuli to the cells under culture conditions. In addition, we use human erythrocytes to produce high-purity and quality EVs for RNA therapy. As erythrocytes are nucleated cells without DNA, EVs produced by this means do not pose a risk of gene transfer.
- Extending circulation time
  To address the insufficient residence time of exogenous EVs in circulation, we surface-modify EVs to avoid detection by the immune system. We extend the circulating half-life and increase their bioavailability to target tissues by coating various anti-phagocytic molecules on therapeutic EVs.
- Improving targeting capability
  Improving the targeting ability of therapeutic EVs can avoid the side effects of drug retention in normal organs and improve therapeutic efficacy. We offer our customers EV surface modifications to enhance their targeting capabilities. This involves the binding of ligands on the surface of vesicles that recognize unique markers or aberrantly expressed proteins on target cells. We also offer a wide range of chemical reactions performed for ligand applications on vesicles, especially regarding cross-linking agents such as polyethylene glycol (PEG).

Our company has the strength to provide customers with expert scientific services and technical support in the design and development of EV-based nucleic acid delivery carriers. If you are interested in our services, please contact us for more details and a quotation.

Reference

Zhao, M. X.; Zhu, B. J. The research and applications of quantum dots as nano-carriers for targeted drug delivery and cancer therapy. Nanoscale Research Letters, 2016, 11(1): 1-9.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

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