Development of 3rd Generation Cocal Envelope Producer Cell Lines for Robust Lentiviral Gene Transfer into Hematopoietic Stem Cells and T Cells

Lentiviral vectors (LVs) are currently considered the gold standard for hematopoietic stem cell (HSC) gene therapy and for immunotherapies with genetically modified T cells. LVs have commonly been pseudotyped with the heterologous vesicular stomatitis virus envelope glycoprotein (VSV-G), which confers broad tropism and stability to the vector. However, VSV-G is inactivated by human serum complement, making it unsuitable for in vivo delivery when vector amount is limiting. The authors of the study has developed and used a cocal vesiculovirus envelope glycoprotein to pseudotype LV. The cocal envelope glycoprotein shares 71.5% identity at the amino acid level with the VSV-G Indiana envelope, and cocal pseudotyped LVs (cocal LVs) were found to have broad tropism and to be more resistant to inactivation by human serum than VSV-G pseudotyped LVs. Here the authors describe the development of high titer 3rd generation self-inactivating (SIN) LV based on the cocal envelope. They designed the protocol and generated a producer cell line for the large scale production of high titer cocal LV. Their results show that Cocal-pseudotyped LVs has a resistance to human serum inactivation and outperform VSV-G vectors in the transduction of human and nonhuman primate CD34+ and CD4+ T cells.

This work is a good drawing of the flexibility of LV pseudotyping. This flexibility can be leveraged to enhance the efficiency of transduction in specific experimental contexts but also to target particular cell types. For example, GEG Tech takes advantage of LV pseudotyping to develop vectors with the Mokola envelope which allows to transduce specifically the astrocytes. Furthermore GEG Tech R&D is developing several other envelopes with attractive features which will be soon available. Keep in touch! 

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