An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor- independent cell entry mechanism

Igor Dmitriev, Victor Krasnykh, C. Ryan Miller, Minghui Wang, Elena Kashentseva, Galina Mikheeva, Natalya Belousova, David T. Curiel

Research output: Contribution to journalArticlepeer-review

662 Scopus citations

Abstract

Recombinant adenoviruses (Ad) have become the vector system of choice for a variety of gene therapy applications. However, the utility of Ad vectors is limited due to the low efficiency of Ad-mediated transfer to cells expressing marginal levels of the coxsackievirus and adenovirus receptor (CAR). In order to achieve CAR-independent gene transfer by Ad vectors in clinically important contexts, we proposed modification of viral tropism via genetic alterations to the viral fiber protein. We have shown that incorporation of an Arg-Gly-Asp (RGD)-containing peptide in the HI loop of the fiber knob domain results in the ability of the virus to utilize an alternative receptor during the cell entry process. We have also demonstrated that due to its expanded tissue tropism, this novel vector is capable of efficient transduction of primary tumor cells. An increase in gene transfer to ovarian cancer cells of 2 to 3 orders of magnitude was demonstrated by the vector, suggesting that recombinant Ad containing fibers with an incorporated RGD peptide may be of great utility for treatment of neoplasms characterized by deficiency of the primary Ad type 5 receptor.

Original languageEnglish
Pages (from-to)9706-9713
Number of pages8
JournalJournal of virology
Volume72
Issue number12
DOIs
StatePublished - Dec 1998

Fingerprint

Dive into the research topics of 'An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor- independent cell entry mechanism'. Together they form a unique fingerprint.

Cite this