Table 3.
Use of PEO-PPO-PEO copolymers for viral gene transfer (part II).
| Viral Systems | Copolymers | Genes | Targets | Administration | Observations | References |
|---|---|---|---|---|---|---|
| rAAV | Pluronic® F127 | GM-CSF | solid tumors | in vivo intratumoral infusion (mouse) | higher efficiency by combining DC, local tumor irradiation and controlled supply of recombinant mGM-CSF with Pluronic® | [77] |
| Pluronic® F68 | lacZ | adipose tissue | in vivo inguinal (mouse) | increased transgene expression after 4 weeks | [78] | |
| Pluronic® F127 | lacZ | cartilage | in vitro hMSCs | controlled release of rAAV for high efficiencies over time and gene expression levels similar to those achieved by direct vector application | [80] | |
| Pluronic® F68, Tetronic® 908 | RFP, lacZ, and SOX9 | cartilage | in vitro hMSCs | encapsulation of rAAV in polymeric micelles for effective, durable, and safe modification of hMSCs; restoration of hMSC transduction in conditions of gene transfer inhibition; effective chondrogenesis | [79] | |
| Pluronic® F68, Tetronic® 908 | lacZ | cartilage | in vitro hOACs in situ human osteochondral model | micellar encapsulation for increased stability and bioactivity of rAAV; high levels of safe transgene expression in vitro and in experimental osteochondral defects in situ | [81] | |
| Pluronic® F68, Tetronic® 908 | TGF-β | cartilage | in vitro hOACs in situ human osteochondral model | increased levels of transgene expression compared with free vector treatment; high proteoglycan deposition and increased cell numbers in hOACs in vitro; high deposition of type-II collagen and reduced hypertrophy in osteochondral defects models in situ | [82] | |
| Pluronic® F68, Tetronic® 908 | lacZ | cartilage | in vitro hMSCs | high concentrations of rAAV; sustained levels of transgene expression over time | [92] |
Abbreviations: rAAV: recombinant adeno-associated viral vectors; lacZ: E. coli β-galactosidase; GM-CSF: granulocyte-macrophage colony-stimulating factor; hMSCs: human mesenchymal stem cells; RFP: red fluorescent protein; SOX9: sex-determining region Y-type high mobility group box 9; hOACs: human osteochondral chondrocytes; TGF-β: transforming growth factor beta.