Retargeting of viral vectors to the folate receptor endocytic pathway

J. A. Reddy, D. Clapp, P. S. Low

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Viral vectors with high transfection efficiencies are not always those with optimal target cell binding specificities. As a consequence, virus pseudotyping has been developed to endow transfection competent viruses with improved cell binding specificities and affinities. We have hypothesized that chemical conjugation of a virus to a cell specific ligand might also alter its target cell specificity and produce a virus that would transfect only the desired cell type. To test this concept, an ecotropic replication-defective myeloproliferative sarcoma retrovirus and an amphotropic murine adenovirus containing the gene for β-galactosidase were chemically derivatized with folic acid. As expected from its strong ecotropism, the unmodified retrovirus did not induce β-galactosidase expression in nonhost KB cells, while the amphotropic adenovirus yielded high levels of gene expression in the same cell line. Surprisingly, although folate derivatization enabled avid binding of both viruses to folate receptor expressing KB cells, the folate conjugation did not promote retroviral gene expression and actually prevented the normal β-galactosidase expression seen with the adenoviral vector. The fact that co-administration of excess free folic acid to block uptake by folate receptor-mediated endocytosis restored adenoviral gene expression to the level obtained with unmodified virus suggests that folate derivatization per se does not hamper viral activity. We, therefore, conclude that neither retroviral nor adenoviral delivery via the folate endocytosis pathway is compatible with viral gene expression in KB cells.

Original languageEnglish
Pages (from-to)77-82
Number of pages6
JournalJournal of Controlled Release
Volume74
Issue number1-3
DOIs
StatePublished - Jul 6 2001

Fingerprint

Folic Acid
Galactosidases
KB Cells
Viruses
Gene Expression
Retroviridae
Endocytosis
Adenoviridae
Transfection
Virus Attachment
Viral Genes
Sarcoma
Ligands
Cell Line
Genes

Keywords

  • Folate receptor
  • Gene delivery
  • Tumor targeting
  • Viral tropism
  • Viral vectors

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Retargeting of viral vectors to the folate receptor endocytic pathway. / Reddy, J. A.; Clapp, D.; Low, P. S.

In: Journal of Controlled Release, Vol. 74, No. 1-3, 06.07.2001, p. 77-82.

Research output: Contribution to journalArticle

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