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 induce stable gene expression in non-dividing tissue cells. However, none of the current gene transfer systems (both viral and non-viral) satisfies this goal. In order to develop a novel gene delivery system that is free from the defects of existing gene transfer vectors, we analyzed natural biological phenomena that involve gene transfer and expression, and made artificial components that mimic the functioning of these systems. Our recent results shed light on three major aspects of gene transfer and expression: (1) the direct delivery of DNA into cytoplasm using fusogenic liposomes, (2) the transfer of DNA from cytoplasm to nucleus with a nuclear localization signal, and (3) the stabilization of DNA in the nucleus as an independent replicon. The possible development of a hybrid vector by combining these components is discussed.
Nakanishi
M
M
Department of Neurovirology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan. mahito@biken.osaka-u.ac.jp
Mizuguchia
H
H
Ashihara
K
K
Senda
T
T
Akuta
T
T
Okabe
J
J
Nagoshi
E
E
Masago
A
A
Eguchi
A
A
Suzuki
Y
Y
Inokuchi
H
H
Watabe
A
A
Ueda
S
S
Hayakawa
T
T
Mayumi
T
T
D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000008:administration & dosage / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008854:Microscopy, Electron; D019913:Nuclear Localization Signals; D018108:Respirovirus / Q000235:genetics*
D019913:Nuclear Localization Signals; D004247:DNA