Altering retroviral tropism using a random-display envelope library

Keith Bupp, Monica J. Roth

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Tissue-specific gene delivery is an important aspect of many gene therapy applications. The experiments reported here constitute the first successful demonstration that cell-specific entry can be obtained by screening a random library of retroviral envelope proteins produced from a mammalian cell system. The library consisted of 106 different subgroup A feline leukemia virus envelope protein variants with 10 randomly substituted amino acids in the receptor-determining region. Selecting the library for fully functional envelope proteins able to mediate stable gene transfer resulted in the identification of a single envelope protein variant (EF). Subsequent examination of the host range of EF revealed that it was highly specific for D17 canine osteosarcoma cells. This was in contrast to the host ranges of the parental subgroup A and closely related subgroup C envelope proteins. Interference assays on D17 cells further indicated that receptor usage by EF was also altered compared with the A and C envelope proteins. The EF envelope protein thus isolated should be useful for studying gene therapy treatments of osteosarcoma in a large-animal model.

Original languageEnglish (US)
Pages (from-to)329-335
Number of pages7
JournalMolecular Therapy
Volume5
Issue number3
DOIs
StatePublished - 2002

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Keywords

  • Feline leukemia virus
  • Gene targeting
  • Gene therapy
  • Peptide library
  • Retrovirus

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