Alphavirus for the Transfection of Tumor Cell Lines
Intratumoral Gene Delivery by Alphavirus
Tumor Targeting of Alphavirus Vectors
Production of Retrovirus-Like Particles by Alphavirus
Safety of Alphavirus Vectors
Conclusions and Future Prospects
Alphavirus vectors can infect a broad range of mammalian cells both in cell cultures and in vivo. The presence of the RNA replicon generates extreme RNA levels in infected cells, which is the basis for the very high levels of heterologous gene expression. Application of replication-deficient vectors leads to short-term expression, which makes these vectors highly attractive for cancer gene therapy. Alphaviruses can be used as vaccine vectors for both prophylactic and therapeutic applications. In this context, the P185 tumor antigen and human papilloma virus gene E7, when administered in mice, resulted in protection against tumor challenge and tumor regression in animals with pre-existing tumors. Alphavirus vectors carrying therapeutic or toxic genes used for intratumoral injections have demonstrated efficient tumor regression. For systemic delivery, expression targeting has been obtained by the introduction of targeting sequences in the envelope structure of the virus. Alternatively, alphavirus particles have been encapsulated in liposome, which can target tumor cells.
Key Words: Alphavirus vectors; cancer vaccines; intratumoral injection; tumor targeting.
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