Pseudotyping of lentiviral vector with novel vesiculovirus envelope glycoproteins derived from Chandipura and Piry viruses

Lentiviral vectors are commonly pseudotyped with the heterologous envelope VSV-G due to its broad host tropism and stability conferred. However, in some cases, the sensibility of VSV-G by human complement hinders the use of lentiviral vectors for broader applications. In this study, the authors evaluated two serologically distinct novel viral envelopes derived from Chandipura (CNV-G) and Piry (PRV-G) vesiculoviruses to pseudotype lentiviral vectors. They showed that these envelopes do not interfere the production of high titer vector stocks and demonstrated the ability of lentiviral vectors CNV-G and PRV-G to transduce different cell types such as epithelial, fibroblast or neuroblast origin cells (GHOST, HeLa, BHK, MDCK and N2a cells) and also non-adherent cells such as lymphocytic lineage (Sup-T1, CEM, Jurkat cells). Finally, they tested the resistance of the different lentiviral vectors to the inactivation by five sera from different donors. While VSV-G pseudotype was inactivated significantly with a 70–80% reduction in the overall titer, the PRV-G pseudotype showed only 10–45% drop and CNV-G pseudotype decreased in titer by 45–65%. Overall, the resistance of CNV-G and PRV-G to serum inactivation relative to that of VSV-G is significant (p<0.05), thus indicating the relative stability of these for in vivo use.  In conclusion, CNV-G and PRV-G pseudotyped vectors are expected to fill a gap when alternative envelope proteins are needed to transduce a particular cell type and when neutralizing immune responses preclude the use of the standard VSV-G pseudotyped vectors for in vivo gene delivery.

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