AN ADENOVIRUS VECTOR WITH GENETICALLY-MODIFIED FIBERS DEMONSTRATES EXPANDED TROPISM VIA UTILIZATION OF A COXSACKIEVIRUS AND ADENOVIRUS RECEPTOR-INDEPENDENT CELL ENTRY MECHANISM
I. Dmitriev et al., AN ADENOVIRUS VECTOR WITH GENETICALLY-MODIFIED FIBERS DEMONSTRATES EXPANDED TROPISM VIA UTILIZATION OF A COXSACKIEVIRUS AND ADENOVIRUS RECEPTOR-INDEPENDENT CELL ENTRY MECHANISM, Journal of virology (Print), 72(12), 1998, pp. 9706-9713
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 gene tran
sfer to cells expressing marginal levels of the coxsackievirus and ade
novirus receptor (CAR). In order to achieve CAR-independent gene trans
fer by Ad vectors in clinically important contexts, we proposed modifi
cation of viral tropism via genetic alterations to the viral fiber pro
tein. We have shown that incorporation of an Arg-Gly-Asp (RGD)-contain
ing peptide in the HI loop of the fiber knob domain results in the abi
lity of the virus to utilize an alternative receptor during the cell e
ntry process. We have also demonstrated that due to its expanded tissu
e tropism, this novel vector is capable of efficient transduction of p
rimary tumor cells. An increase in gene transfer to ovarian cancer cel
ls of 2 to 3 orders of magnitude was demonstrated by the vector, sugge
sting that recombinant Ad containing fibers with an incorporated RGD p
eptide may be of great utility for treatment of neoplasms characterize
d by deficiency of the primary Ad type 5 receptor.