Table 1.
Exosome-mediated in vivo delivery of therapeutically relevant siRNAs.
| Donor Cell Type | siRNA Cargo | Exosome Loading Procedure | Administration Route | Target Organ | Effect | Ref. |
|---|---|---|---|---|---|---|
| Cancer | ||||||
| HEK293-T cells overexpressing an iRGD peptide fused with Lamp2b | siRNA to KRAS | cell transfection with siRNA | i/v | A549 cell-based mouse tumor xenograft. | specific targeting of iRGD-exosomes to tumor tissues, strong inhibition of tumor growth | [160] |
| Autologous breast cancer cells | siRNA to S100A4 | CBSA/siRNA nanoparticles were first prepared by incubation. Then, CBSA/siRNA were coated by exosomal membrane, by incubation and extrusion method | intravenously (i/v) | mouse lung metastasis | decrease in metastatic nodules. S100A4 (metastasis-related protein) silencing, by Western blot analysis and fluorescence microscopy. | [161] |
| HEK293-T cells | siRNA to c-Met | cell transfection with siRNA | i/v | gastric tumor mouse xenograft | decrease in expression of c-Met (a key driver for carcinogenesis) | [162] |
| PANC-1 cells | siRNA to PAK4 | electroporation | intra-tumoral injection | PANC-1 mouse tumor xenograft | reduced tumor growth and enhanced mice survival, decrease in PAK4 (a driver of pancreatic cancer progression) by IHC staining of tumors. | [120] |
| HEK293-T cells overexpressing a human IL3 fragment fused with Lamp2b | siRNA to BCR-ABL | cell transfection with siRNA | intraperitoneal injection | CML mouse xenograft | slower tumor growth, reduction in BCR-ABL mRNA | [163] |
| MSCs | siRNA to GRP78 | cell transfection with siRNA | injection around the tumor, introperitoneal injection | HCC mouse xenograft and metastasis | inhibition of the growth and metastasis of the cancer cells. | [164] |
| Neurological disorders | ||||||
| Dendritic cells overexpressing RVG peptide fused to Lamp2b | siRNA to BACE1 | electroporation | i/v | mouse brain | 62% knockdown of BACE1, a therapeutic target in Alzheimer’s disease | [94] |
| U87 cells | cholesterol-conjugated siRNA to Huntingtin mRNA | incubation at 37 °C | unilateral infusion into striatum | mouse striatum | silencing of up to 35% of Huntingtin mRNA, a target of Huntington disease | [165] |
| MSC | siRNA to CTGF | electroporation | i/v | rat injured spinal cord (ISC) | significant decrease in CTGF expression in ISC segment, with reductions in inflammation and neuronal apoptosis | [166] |
| HEK293-T cells overexpressing RVG peptide fused to Lamp2b | siRNA to HMGB1 | electroporation | i/v | ischemic stroke model by middle cerebral artery occlusion (MCAO) | decreases in: HMGB1; tumor necrosis factor-α (TNF-α); apoptosis; and size of affected brain region | [119] |
| Primary rat corticalneuronal cultures | siRNA to ASC | electroporation | femoral artery injection | rat ISC | knockdown of ASC protein levels by approx. 76%, decrease in caspase-1 activation and processing of IL-1β after SCI. | [167] |
| Dendritic cells overexpressing RVG peptide fused to Lamp2b | siRNA to Alpha-synuclein | electroporation | i/v | mouse brain | decrease in alpha-synuclein expression (a target of Parkinson disease) in normal and S129D a-Syn transgenic mice | [168] |
| HEK293-T cells overexpressing RVG peptide fused to Lamp2b | siRNA to MOR opioid receptor | cell transfection with siRNA | i/v | mouse brain | reducing in MOR mRNA and protein, with inhibition of morphinerelapse | [169] |
| Infection | ||||||
| Huh7 cells | siRNA to CD81 | transfection of shRNA-encoding plasmid | i/v injection of 100-fold concentrated shCD81Huh7 -conditioned medium | mouse liver | 20% reduction in cell surface expression of CD81, a HCV receptor | [153] |