Viruses have evolved specialized molecular mechanisms to transfer their genome efficiently into host cells. Viruses can be repurposed into viral vectors to achieve controlled gene transfer to desired cells. One of the most popular class of vectors, lentiviral vectors, transduce mammalian cells efficiently. Lentiviral vectors are pseudotyped with various heterologous viral envelopes to alter their tropism. While the most common example is the envelope glycoprotein from vesicular stomatitis virus (VSVG), many other viral proteins have also been used. Pseudotyping lentiviral vectors with a diverse set of naturally occurring or engineered viral envelopes has allowed targeted infection of specific cell types. Many exciting studies are further uncovering new specificities and shortcomings of pseudotyped lentiviral vectors. These studies will expand the toolbox to make lentiviral vectors that cater to the specific requirements of transduction. In this review, we provide a comprehensive overview of various viral envelope pseudotypes used with LVs, their specificity, advantages, and drawbacks
