Abstract
In the current study, the construction of a plasmin-activatable epidermal growth factor (EGF)receptor targeted vector is described. The 52 amino acid EGF-receptor binding domain was linked to codon + 1 of the N- terminus of the 4070A envelope glycoprotein (SU) via a PSIQYRGL (single letter amino acid code) plasmin-sensitive linker. The plasmin-cleavable vector gave low background infectivity on EGF-receptor positive human epithelial carcinoma A431 cells but was efficiently activated by endogenous proteases on EGF-receptor positive human fibrosarcoma HT1080 cells. Addition of exogenous plasminogen to the A431 cells increased the infectivity of the Er-.WSN.A vector up to 12-fold and this plasmin-dependent increase in infectivity of the vector could be suppressed by addition of aprotinin, a serine protease inhibitor.
Original language | English (US) |
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Pages (from-to) | 112-120 |
Number of pages | 9 |
Journal | Tumor Targeting |
Volume | 3 |
Issue number | 2 |
State | Published - 1998 |
Keywords
- 4070A-MLV
- A431
- Aprotinin
- Epidermal growth factor
- Gene delivery
- HT1080
- Plasmin
- Plasminogen
- Retrovirus
ASJC Scopus subject areas
- Pharmacology
- Cancer Research