GENE-TRANSFER VECTORS BASED ON SENDAI VIRUS

A gene delivery system is a fundamental technology used in human gene therapy. In order to treat patients suffering from incurable metabolic diseases, we must be able to deliver genes efficiently in situ and in duce stable gene expression in non-dividing tissue cells. However, non e of the current gene transfer systems (both viral and non-viral) sati sfies this goal, in order to develop a novel gene delivery system that is free from the defects of existing gene transfer vectors, we analyz ed natural biological phenomena that involve gene transfer and express ion, and made artificial components that mimic the functioning of thes e systems. Our recent results shed light on three major aspects of gen e transfer and expression: (1) the direct delivery of DNA into cytopla sm using fusogenic liposomes, (2) the transfer of DNA from cytoplasm t o nucleus with a nuclear localization signal, and (3) the stabilizatio n of DNA in the nucleus as an independent replicon. The possible devel opment of a hybrid vector by combining these components is discussed. (C) 1998 Elsevier Science B.V.