Strategies for Selective Amplification

As briefly mentioned above, conditionally replicative adenoviruses (CRAds) have great potential in the field of cancer gene therapy (48,49,62). Cancer gene therapy requires tumor-wide therapeutic effect in a vast majority of the cancer cells. In this context, infectivity-enhanced CRAds can achieve such wide spread effect by spreading to the surrounding cancer cells via viral progeny infection (18,19,67). Because each tumor type requires different targeting methods, both transductional and transcriptional targeting need to be developed and optimized for each CRAd for each individual disease context.

Another interesting idea is to use CRAds as a modality to support the amplification of E1-deleted vectors in target cells. Alemany et al. showed that a gutless vector conditionally expressing the E1 gene and an E1-deleted vector can trans-complement each other and replicate (95). In another case, an E1B55k-deleted conditionally replicative virus was combined with a replication-incompetent interleukin-12 expression vector, enhanced antitumor effect was observed as a result of dramatically augmented interleukin-12

expression (96). Although precise control of replication of each virus may be difficult, this system is relatively easy to construct and provides large cloning capacity. In this meaning, the versatility of this system may lead to interesting vector systems in the future.

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