Cell-type-specific gene delivery into neuronal cells in vitro and in vivo.
The avian retroviruses reticuloendotheliosis virus strain A (REV-A) and spleen necrosis virus (SNV) are not naturally infectious in human cells. However, REV-A-derived viral vectors efficiently infect human cells when they are pseudotyped with envelope proteins displaying targeting ligands specific for human cell-surface receptors. Here we report that vectors containing the gag region of REV-A and pol of SNV can be pseudotyped with the envelope protein of vesicular stomatitis virus (VSV) and the glycoproteins of different rabies virus (RV) strains. Vectors pseudotyped with the envelope protein of the highly neurotropic RV strain CVS-N2c facilitated cell type-specific gene delivery into mouse and human neurons, but did not infect other human cell types. Moreover, when such vector particles were injected into the brain of newborn mice, only neuronal cells were infected in vivo. Cell-type-specific gene delivery into neurons may present quite specific gene therapy approaches for many degenerative diseases of the brain.
D000818:Animals; D001921:Brain / Q000166:cytology / Q000821:virology; D002460:Cell Line; D006224:Cricetinae; D004285:Dogs; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000821:virology*; D011820:Rabies virus / Q000235:genetics / Q000378:metabolism; D017986:Reticuloendotheliosis Viruses, Avian / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D012192:Retroviridae Infections / Q000821:virology; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins
D014759:Viral Envelope Proteins