Cells already ship RNA to each other in tiny natural parcels. Extracellular vesicles turn that biological postal service into a delivery vehicle that the body recognises as its own.
- Size range
- 30–1000 nm
- Origin
- Cell-derived
- Strength
- Crosses tough barriers
Extracellular vesicles (EVs) are membrane-bound particles released by almost every cell. Once dismissed as cellular debris, they are now known to carry proteins, lipids and nucleic acids between cells as a natural communication system.
Researchers are now harnessing them as next-generation carriers. EVs mark a shift from synthetic systems such as lipids and polymers towards bio-inspired, cell-derived nanocarriers that mimic natural processes.
Because they come from cells, EVs are inherently biocompatible and can cross barriers such as the blood–brain barrier that stop most synthetic carriers, which makes them one of the most promising non-viral vectors for both in vitro and in vivo use.
Types of vesicle and what they carry
Exosomes (30–150 nm)
Formed inside multivesicular bodies and released when these fuse with the cell surface; the most used for delivery.
Microvesicles (100–1000 nm)
Bud directly outwards from the plasma membrane.
Apoptotic bodies (>1000 nm)
Released during programmed cell death; rarely used for transfection.
Natural cargo
mRNA, miRNA and other RNAs, DNA fragments, proteins such as tetraspanins, and lipids.
How it works
- 1
Production and isolation
EVs are harvested from cultured cells such as HEK293, mesenchymal stem cells or dendritic cells by ultracentrifugation or size-exclusion chromatography.
- 2
Cargo loading
Either the parent cell is engineered to package the RNA, or purified EVs are loaded by electroporation, sonication or extrusion.
- 3
Targeting and uptake
Surface proteins, natural or engineered such as Lamp2b fusions, bind the recipient cell, which takes the EV in by endocytosis or fusion.
- 4
Cargo release
Inside the cell, the cargo silences genes, expresses proteins or edits the genome.
Where EVs come from
| Source | Why it is used |
|---|---|
| HEK293 cells | High yield and easy to engineer; widely used for mRNA and siRNA delivery |
| Mesenchymal stem cells | Anti-inflammatory and regenerative; suited to in vivo therapy |
| Dendritic cells | Immune-stimulating; explored in cancer vaccines |
| Plants | Low cost, scalable and non-immunogenic; emerging for oral delivery |
| Engineered cells | Display ligands such as RVG to reach the brain, or load cargo more efficiently |
Strengths
- Natural biocompatibility. Derived from mammalian cells, so toxicity and immune recognition are low.
- Built-in targeting. Inherit surface markers from parent cells; MSC-derived EVs home to inflamed tissue.
- Cross biological barriers. Pass the blood–brain barrier, placenta and dense tumour stroma.
- Stable in circulation. The lipid bilayer protects cargo from nucleases and extends half-life.
- Multi-cargo. Co-deliver RNA, DNA, proteins and small molecules in one vesicle.
- Scalable. Bioreactor culture and better purification enable larger-scale production.
Challenges
- Low loading efficiency. Passive loading yields little cargo, and active loading can damage vesicles.
- Heterogeneity. Size, cargo and surface markers vary between batches.
- Isolation and purification. Needs specialised equipment and expertise for high purity.
- Cost of GMP production. Large-scale, GMP-compliant processing remains expensive.
- Standardisation. Isolation, characterisation and potency methods are still being harmonised under MISEV guidelines.
- Limited targeting control. Precise targeting usually requires engineering the parent cells.
Where it is used
Gene silencing
siRNA or miRNA to knock down disease-related genes such as oncogenes.
mRNA therapy
Transient protein expression for vaccination, enzyme replacement or reprogramming.
CRISPR delivery
Cas9 RNPs delivered with fewer off-target effects.
Neurodegenerative disease
Brain-targeted delivery of therapeutic RNAs across the blood–brain barrier.
Regenerative medicine
Stem cell EVs promote tissue repair and calm immune responses.
Cancer and vaccines
Tumour-suppressor miRNAs, or vesicles presenting antigens and adjuvants.
What comes next
EV research is moving towards precision-engineered vesicles, supported by regulators such as the FDA and EMA and growing investment in EV biomanufacturing.
Designer EVs
CRISPR-edited parent cells optimise loading, targeting and immune evasion.
Hybrid EVs
EVs fused with liposomes or synthetic nanoparticles.
EV mimetics
Synthetic vesicles that copy EV structure at lower cost and higher consistency.
Off-the-shelf therapies
Allogeneic, GMP-compliant EV products for scalable gene therapy.
EVs mark a shift from synthetic, foreign carriers to nature-inspired delivery, combining biocompatibility, targeting potential and functional nucleic acid delivery for research and the clinic.