LVV Approaches To Pseudotyping And Plasmid Design

Innovative cell & gene therapies are providing unprecedented advancements in treating diseases, and lentiviruses (LVs) have emerged as the go-to vectors for these products, delivering accurate genetic material to target cells to treat a wide range of medical conditions. As researchers consider the design of their lentiviral vector (LVV), pseudotyping the LV and plasmid selection play critical roles in determining the treatment’s efficacy in targeting specific cells and potential cytotoxicity.

Since LVVs demonstrate a natural tropism for CD4-expressing cells, the virus is pseudotyped with alternative envelope glycoproteins to target cells lacking CD4 receptors, increasing transduction efficiency. VSV-G, the most commonly pseudotyped envelope protein which is widely acknowledged for its high performance standard, is also linked to cytotoxicity and can be inactivated by the complement system. This complication necessitates further consideration and design to achieve optimal results in therapies.

Proper plasmid design involves efficient incorporation of the transgene into the host genome while also ensuring safety. But developers must also consider the “packaging plasmids” to ensure increased titer and safety and that all unnecessary and potentially burdensome viral sequences are removed. Designing the plasmid as well as the downstream processes requires careful consideration of the pseudotype, as many pseudotypes are sensitive to particular physico-chemical conditions. Examine the importance of pseudotyping for increasing transduction efficiency and how advanced knowledge and consideration can lead to a safe and highly targeted product.