Retroviral gene delivery system activatable by plasmin

Kah-Whye Peng, F. J. Morling, F. L. Cosset, Stephen J Russell

Research output: Contribution to journalArticle

22 Scopus citations

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 languageEnglish (US)
Pages (from-to)112-120
Number of pages9
JournalTumor Targeting
Volume3
Issue number2
StatePublished - 1998

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Keywords

  • 4070A-MLV
  • A431
  • Aprotinin
  • Epidermal growth factor
  • Gene delivery
  • HT1080
  • Plasmin
  • Plasminogen
  • Retrovirus

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology

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