Oncolytic adenoviruses expressing E1B-156R isoform gene

摘要

The invention relates to a recombinant adenovirus that has an oncolytic effect in a cancer cell. By modulating the level and type of splice isoforms of the E1B gene product, expressed from the E1B gene, the oncolytic activity of such viruses can be enhanced. The invention provides a recombinant adenovirus in which the proportion of the E1B-156R isoform is increased relative to wild-type levels. Such a recombinant adenovirus may selectivity replicate in cancer cells, thereby killing cancer cells, whilst sparing normal cells. Methods of forming the oncolytic adenovirus by modifying the sequence of the E1B gene to increase the level of the E1B-156R isoform are also claimed, along with methods of treating cancer using the aforementioned recombinant adenoviruses. The adenovirus with increased proportions of E1B-156R isoform may have a mutated splice recognition region, preferably at the E1B-93R splice site.