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| Figure 7: Potential modes of action of sscFvPRO140. (a) sscFvPRO140 binds to CCR5 intracellularly. Co-expression of sscFvPRO140 and CCR5 in the same cell could result in binding of sscFvPRO140 to CCR5 in the rER. The binding immunoglobulin protein (BIP) may bind to the sscFvPRO140/CCR5 complex and retain it in the rER, resulting in diminished surface expression of CCR5 and stronger inhibition of R5 HIV entry in the gene-modified compared to unmodified target cells. (b) sscFvPRO140 binds to CCR5 extracellularly. The sscFvPRO140 is secreted and masks surface CCR5, which prevents R5 HIV entry. If CCR5+ HIV target cells are used to secrete sscFvPRO140, the sscFvPRO140 could bind to surface CCR5 on genemodified target cells upon release from the cell. |
