25-10-2012, 10:52 AM
Development and Pre-Clinical Evaluation of a Novel Prostate-Restricted Replication Competent Adenovirus-AD-IU-1
ABSTRACT
Recently we generated a prostate specific chemic promoter, called PSES, by combining the active prostate specific
enhancers from PSA and PSMA genes which are prominently expressed in androgen independent prostate cancers. The goal
of this research is to develop a novel therapeutic agent, Ad-lu-1, using PSES to control the replication of adenovirus and the
expression of a therapeutic gene, herpes simplex thymidine kinase. Due to the size limitation of adenoviral vector, we need
to shorten the size of PSES enhancer. In the past year, we have successfully shorten PSES from 513 bp to 407 bp and made
a pAd-lU-1 cosmid vector as described in the original proposal. After releasing the adenoviral genome by Pac I digestion,
pAd-lu-1 failed to produce an adenovirus. We believe that the size of the recombinant adenoviral genome is still too big to
be packed. While we had a difficult time to make Ad-lu-1, we developed another PSES-E4 based replicative adenovirus and
switched our viral construction strategy. By utilizing adenoviral E4 region, we made our Ad-lu-1, by putting Ela and E4 under
the control of PSES and Elb and TK under the control of shortened PSES (called m6).We are currently characterizing Ad-lu-1.