COMPOSITION AND METHODS FOR CREATING SYNGENEIC RECOMBINANT VIRUS-PRODUCING CELLS

摘要

Replication-defective viruses and means for intracellular replication thereof are described which are useful for gene therapy. Human cells can be changed into recombinant replication-defective virus particle-producing cells by the simultaneous delivery to those cells of two different nucleic acids: the first being a replication-defective viral genome, the second being a nucleic acid that complements the viral sequences deleted from the first nucleic acid so as to result in the production of new infective virus. The first nucleic acid can be delivered by the replication-defective virus itself or, as a nucleic acid that is not part of the virus. In a preferred embodiment, the replication-defective virus includes elements to maintain the two nucleic acids in combination during transduction. Examples of preferred viral sources are adenoviruses, herpesvirus, retroviruses, and adeno-associated viruses. Nucleic acids useful for gene therapy include those that code for proteins used to identify cells infected with the recombinant virus, those that encode for proteins that function to kill cells containing the viral genome, or that encode for therapeutic proteins that will serve to treat a pathophysiologic condition within the body.