Use of spliceosome mediated RNA trans-splicing to confer cell selective replication to adenoviruses

摘要

The present invention provides methods and compositions for conferring tumor selective cell death on cancer cells expressing specific target precursor messenger RNA molecules (cancer cell selective target pre-mRNAs). The compositions of the invention include conditionally replicative adenoviruses that have been genetically engineered to express one or more pre-trans-splicing molecules (PTMs) designed to interact with one or more cancer cell target pre-mRNA and mediate a trans-splicing reaction resulting in the generation of novel chimeric RNA molecules (chimeric RNA) capable of encoding adenovirus specific protein(s). Adenovirus specific proteins include those proteins complementing an essential activity necessary for replication of a defective adenovirus. The methods and compositions of the invention may be used to target a lytic adenovirus infection to cancer cells thereby providing a method for selective destruction of cancer cells. In addition, the adenoviruses of the invention may be engineered to encode PTMs designed to interact with target pre-mRNAs encoded by infectious agents within a cell, thereby targeting selective destruction of cells infected with such agents.