Modification of adenoviral vectors with polyethylene glycol modulates in vivo tissue tropism and gene expression

Sean E. Hofherr, Elena V. Shashkova, Eric A. Weaver, Reeti Khare, Michael A. Barry

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Polyethylene glycol (PEG) is a hydrophilic polymer that has been used to coat adenoviral (Ad) vectors to improve their pharmacology. To analyze the effects of PEG on Ad5 tropism, Ad5 was covalently modified with different sizes of PEG and in vitro and in vivo transduction was analyzed. All tested PEGs ablated in vitro transduction. When protein C (PC) and factors VII, IX, and X were added, only factors IX and X increased transduction by the PEGylated vectors with the largest effect by X. Inactivation of these factors with warfarin drastically reduced liver transduction in mice by the PEGylated vectors after intravenous (IV) injection. Ad5 conjugated with 5 kd PEG maintained normal liver transduction while conjugation with larger 20 and 35 kd PEGs significantly reduced liver transduction. When intraperitoneal (IP) injection was tested, Ad transduced the peritoneum efficiently with only low level liver transduction. When Ad5 was modified with 5 kd PEG, peritoneal transduction was reduced and the virus preferentially transduced the liver. These data demonstrate the effects of different sizes of PEG on in vivo Ad tropism and suggest that this approach may be useful in retargeting and detargeting Ad in vivo.

Original languageEnglish (US)
Pages (from-to)1276-1282
Number of pages7
JournalMolecular Therapy
Volume16
Issue number7
DOIs
StatePublished - Jul 2008

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Tropism
Gene Expression
Liver
Factor X
Factor IX
X Chromosome Inactivation
Factor VII
Peritoneum
Warfarin
Protein C
Intraperitoneal Injections
Intravenous Injections
Polymers
Pharmacology
Viruses

ASJC Scopus subject areas

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

Cite this

Modification of adenoviral vectors with polyethylene glycol modulates in vivo tissue tropism and gene expression. / Hofherr, Sean E.; Shashkova, Elena V.; Weaver, Eric A.; Khare, Reeti; Barry, Michael A.

In: Molecular Therapy, Vol. 16, No. 7, 07.2008, p. 1276-1282.

Research output: Contribution to journalArticle

Hofherr, Sean E. ; Shashkova, Elena V. ; Weaver, Eric A. ; Khare, Reeti ; Barry, Michael A. / Modification of adenoviral vectors with polyethylene glycol modulates in vivo tissue tropism and gene expression. In: Molecular Therapy. 2008 ; Vol. 16, No. 7. pp. 1276-1282.
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