Extracellular Vesicle Development Service

Development of Extracellular Vesicles for Gene Delivery

Extracellular vesicles (EVs), which have emerged as promising vehicles for the delivery of nucleic acid-based therapeutics, are cell-derived naturally coated phospholipids known as nanovesicles which are responsible for biologically important functions. These have sparked interest towards using them for the delivery of RNA for interference as well as for gene therapy. The main interest of our company is EVs as gene therapy delivery vehicles and recent advances in EV engineering that enable us to provide our clients with efficient EV-based gene therapies for precision treatment of rare diseases.

Background

EVs which include exosomes and microvesicles are important for the biomolecule transport phenomenon in an organism including the transport system for nucleic acids such as mRNA. EVs as a therapeutic modality have recently gained attention because of their remarkable biocompatibility, ability to penetrate physiological barriers, and low immunogenicity. Recent works have developed electroporation methods for loading siRNAs into EVs which enables gene silencing effects without a biological toxic effect. This indicates the possibility of developing non-viral vector with enhanced effectiveness and minimal side effects.

Despite the numerous barriers which must be addressed before we can rely on EV-based delivery systems in humans, EVs are more biocompatible and have fewer adverse effects than lipid nanoparticles (LNPs) and adeno-associated viruses (AAVs), which makes them more appealing for use in gene therapy. EVs possess natural biological utility because they are produced by most cell types, which means they can help address an array of human diseases, including some rare ones, as non-invasive diagnostic, prognostic, and therapeutic agents.

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
To facilitate our customers, we provide them with services such as electron microscopy, Western blotting, immunofluorescence, flow cytometry, and other methods for EVs characterization.
EV therapeutic engineering
We offer two ways to load nucleic acids into EVs.
- EV loading methods
  Pseudomonas aeruginosa therapeutic drugs can be loaded into purified EVs by several methods. Generally, large nucleic acids are incorporated into EVs by exosomes fusion with liposomes, themselves hybrided with liposomes. This process creates a liposome capable of bearing and an EV s‘ capable of integrating with and penetrating target cells.
- Parental cell-based engineering
  To solve the problem of low loading efficiency of modifying several macromolecules, modified donor cells were engineered to secrete modified EVs. Specific packages like TAMEL for active and selective RNA incorporation into EVs and EXOtic, a parental cell based mRNA incorporation strategy for targeted RNA delivery, are made available.
Improvement of EV gene delivery systems
Our scientists have devised a number of approaches which facilitate the engineering of natural EVs, thereby improving the outcomes of gene therapy. In particular, we focus on:
- Increasing EV production
  The adopted EV isolation method was inefficient and led towards a high nucleated cell count. Hence, we implement several external stimuli to the cells under culture conditions in order to increase the EV yield. Furthermore, we use human erythrocytes to obtain high-purity and quality EVs intended for RNA therapy because erythrocytes are nucleated cells lacking DNA. EVs produced this way have no gene transfer risks.
- Extending circulation time
  We avoid exogenous EVs circulation detection by the immune system using surface modification to implement changes to EVs aimed at improving their retention time in circulation. The property of rapidly being eradicated from the body is termed as half-life, and circulating anti-phagocytic molecules which are bone therapeutical EVs extend this further, resulting in increased retention by the target tissues.
- Improving targeting capability
  We provide EV surface modification services for our clients which improves targeting of the EVs. This is done by the attachment of ligands to the surface of vesicles that have the ability to bind to unique markers or misexpressed proteins found on the surface of the desired cells. We also provide a substantial number of chemical operations done for vesicle ligand modification, particularly for crosslinking agents like polyethylene glycol (PEG).

Our strong point is to be able to provide customers with specialized scientific assistance and technical services in the design and development of EV-based nucleic acid delivery systems. 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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