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. 2024 Mar 11;14(5):2265–2289. doi: 10.7150/thno.93115

Table 4.

Therapeutic applications under investigation for mRNA encapsulated EVs.

Indication Nanoparticle Cell Source mRNA cargo Loading Method Significance Source
Cancer Breast
(HER2+)
Extracellular Vesicles HEK293 HChrR6 Transfection Demonstrated EV-mediated delivery of functional exogenous mRNA to tumors. 116
Breast
(HER2+)
Extracellular Vesicles HEK293 HChrR6 Transfection Loaded EVs with in vitro transcribed mRNA to avoid the use of plasmids. 119
Breast
(HER2+)
Extracellular Vesicles HEK293 GSDMD-N Transfection Induced pyroptosis in cancer cells through EV-targeted mRNA delivery. 121
Colon, Melanoma Outer MembraneVesicles E. coli EGFP, OVA, or ADPGK Transformation Built an OMV-based mRNA delivery platform to elicit antitumor immunity. 123
Glioma Exosomes MSCs yCD::UPRT Transduction Demonstrated tumor cell internalization of exosomes with mRNA for a suicide gene. 117
Glioma Exosomes MEFs, DCs PTEN Transfection Restored tumor-suppressor function utilizing mRNA-containing exosomes. 122
Glioma Small Extracellular Vesicles MEFs, HEK293T IFN-γ Transfection Induced antitumor activities utilizing immunogenic sEVs. 148
Pancreatic Extracellular Vesicles MEFs, MSCs TP53 Transfection Suppressed tumor growth and increased survival with mRNA loaded EVs. 149
CardiovascularDisease Atherosclerosis (Inflammation) Exosomes HEK293T IL-10 Transfection Controlled inflammation through exosome-based delivery of functional mRNA. 130
Cerebral ischemia Exosomes HEK293 NGF Transfection Delivered mRNA loaded exosomes with therapeutic effects to infarcted regions. 136
Hypercholesterolemia (familial) Exosomes AML12 Ldlr Transfection Restore LDL receptor expression through exosome-based mRNA delivery. 133
Hypercholesterolemia Extracellular Vesicles HEK293T Ldlr Transfection Proposed strategy to improve loading and release of therapeutic mRNA in EVs. 134
Infectious disease COVID-19 Extracellular Vesicles LSCs GFP Electroporation Enhanced pulmonary bioavailability and therapeutic efficacy with lung derived EVs. 115
COVID-19 Extracellular Vesicles LSCs SARS-CoV-2 spike protein Electroporation Demonstrated EV-based inhaled mRNA drug-delivery system superior to LNPs. 125
HIV-1 Exosomes HEK293T ZPAMt Transfection Epigenetically repressed HIV-1 infection through exosome-mediated mRNA delivery. 127
NeurologicalConditions Parkinson's
disease
Exosomes HEK293T Catalase Transfection Reduced neurotoxicity and neuroinflammation through exosome-based mRNA delivery. 118
Other Inflammatory bowel
disease
Extracellular Vesicles HEK293T GFP, PGC1α, or IL-10 Transfection Proposed strategy to improve loading of therapeutic mRNA in EVs for gene therapy. 154
Obesity Exosomes HEK293T Luciferase or PGC1α Transfection Enhanced efficacy and minimized off-target effects with exosome-based mRNA delivery. 155
Obesity Exosomes HEK293T Bmp7 Transfection Induced white adipose tissue browning though exosome-mediated mRNA delivery. 156
Photoaged skin Extracellular Vesicles nHDFs COL1A1 Transfection Achieved EV-mediated intradermal mRNA delivery for protein-replacement therapy. 143