Autotransduction and Pseudotyping as a Key Limitations in Lentiviral Vector Production

Lentiviral vectors are one of the important tools used in gene and cell therapy. Vector production involves a process known as pseudotyping, whereby glycoproteins originally derived from other viruses are incorporated into the envelope of the vector. The production of lentiviral vectors is associated with the risk of autotransduction. This phenomenon can cause genetic changes in the producer cells, loss of vector particles, and overproduction of transgenic proteins. This review article presents the phenomenon of autotransduction and the factors that influence its intensity. The review focuses on various viral envelopes, as different pseudotypes have been observed to interact differently with entry receptors. In addition to the classical VSV-G pseudotype, attention has also been directed toward alternative pseudotypes and viral envelopes, including GALV, BaEV, HERV-W, CNV-G, PRV-G, HA Rostock, Sendai virus, Sindbis virus, KoRV, LCMV, NiV, and RD114-pro. Particular emphasis has been placed on the low-density lipoprotein receptor, which is currently the most thoroughly characterized viral entry receptor. Furthermore, this review explores strategies aimed at minimizing autotransduction. In addition, we highlight key areas that warrant further investigation regarding lentiviral vector production.