Development of novel simian immunodeficiency virus vectors carrying a dual gene expression system.
The development of highly efficient and safe gene transfer methods suitable for clinical use is required for human gene therapies. We have developed a novel lentiviral vector system, based on the nonpathogenic simian immunodeficiency virus from African green monkeys (SIVagm), that carries a unique dual gene expression system. This system utilizes the lentivirus Rev responsive element (RRE). Self-inactivating vectors were also developed by deleting a U3 region in the 3' long terminal repeat (3' LTR) of the virus. When pseudotyped with a vesicular stomatitis virus envelope glycoprotein G (VSV-G), the SIVagm-based vectors could transduce both growth-arrested human cells and terminally differentiated neuronal cell lines. Using these vectors, two reporter genes could be expressed simultaneously at equal levels, and expression levels of both genes could be altered by modifying the length of the RRE sequence. These SIVagm-based vectors might offer safety advantages over other lentivirus-based vectors. Furthermore, the novel dual gene expression system described here could increase the usefulness and value of both viral and nonviral vectors in gene therapy.
Nakajima
T
T
DNAVEC Research, Inc., Tsukuba, Ibaraki 305-0856, Japan.
Nakamaru
K
K
Ido
E
E
Terao
K
K
Hayami
M
M
Hasegawa
M
M
D001483:Base Sequence; D002460:Cell Line / Q000821:virology; D005786:Gene Expression Regulation; D015694:Gene Products, rev / Q000235:genetics; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D020218:Response Elements / Q000235:genetics; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D020079:Terminal Repeat Sequences; D014759:Viral Envelope Proteins / Q000235:genetics
C028391:G protein, vesicular stomatitis virus; D015694:Gene Products, rev; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins