1. ¹Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
2. ²Department of Internal Medicine, Division of Infectious Diseases, and Translational Immunovirology Program, Mayo Clinic, Rochester, Minnesota, USA
3. ³Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, Minnesota, USA
4. ⁴Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA
5. ⁵Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA

Correspondence: Michael A. Barry, Mayo Clinic 200 First Street SW, Rochester, Minnesota, USA. E-mail: mab@mayo.edu

Received 25 January 2008; Accepted 1 April 2008; Published online 6 May 2008.

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.