Original Article
Subject Categories: Vector Engineering and Delivery
Molecular Therapy (2007) 15, 566–570. doi:10.1038/sj.mt.6300044; published online 19 December 2006
Modulation of Adenoviral Transduction In Vitro and In Vivo by Hyaluronan and its Receptor CD44
Saumya R Chaudhuri1,6,7, Joshua N Mallam1,7, Patricia Chévez-Barrios2,3, Lalita Wadhwa1, Philip Ng4, Mary Y Hurwitz1 and Richard L Hurwitz1,3,5
- 1Department of Pediatrics, Texas Children's Cancer Center and Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA
- 2Department of Pathology, The Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA
- 3Department of Ophthalmology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA
- 4Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
- 5Department of Molecular and Cellular Biology, Texas Children's Cancer Center and Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA
Correspondence: Richard L Hurwitz, Department of Pediatrics, MC 3-3320, Baylor College of Medicine, 6621 Fannin St, Houston, Texas 77030-2399, USA. E-mail: rhurwitz@bmc.tmc.edu
6Current address: Institute of Microbial Technology, Sector 39A, Chandigarh –160036, India
7These authors contributed equally to this work
Received 27 June 2005; Accepted 4 September 2006; Published online 19 December 2006.
Abstract
Adenovirus infection is a significant cause of ocular, respiratory, and gastrointestinal illness and can spread rapidly. Morbidity is considerable in immune-suppressed individuals and there is significant mortality. There are no effective therapies. During preclinical studies of adenoviral-mediated gene therapy for ocular disorders, we noticed a significant increase in transduction when the target cells were exposed to adenovirus in the presence of ocular vitreous. The vitreous is mainly comprised of water, collagen, and the large polysaccharide hyaluronan. In this paper, we report data that implicate hyaluronan in the adenoviral infectious process and show that interference with the interaction between hyaluronan and its cellular receptor CD44 can block adenovirus transduction in vitro and in vivo.
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