Abolishing Retro-Transduction of Producer Cells in Lentiviral Vector Manufacturing

Viruses. 2024 Jul 29;16(8):1216. doi: 10.3390/v16081216.

Abstract

Transduction of producer cells during lentiviral vector (LVV) production causes the loss of 70-90% of viable particles. This process is called retro-transduction and it is a consequence of the interaction between the LVV envelope protein, VSV-G, and the LDL receptor located on the producer cell membrane, allowing lentiviral vector transduction. Avoiding retro-transduction in LVV manufacturing is crucial to improve net production and, therefore, the efficiency of the production process. Here, we describe a method for quantifying the transduction of producer cells and three different strategies that, focused on the interaction between VSV-G and the LDLR, aim to reduce retro-transduction.

Keywords: LDL receptor; VSV-G pseudotyping; gene therapy; lentiviral vector; lentiviral vector manufacturing; retro-transduction.

MeSH terms

  • Genetic Vectors* / genetics
  • HEK293 Cells
  • Humans
  • Lentivirus* / genetics
  • Membrane Glycoproteins
  • Receptors, LDL* / genetics
  • Receptors, LDL* / metabolism
  • Transduction, Genetic*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism

Substances

  • Receptors, LDL
  • Viral Envelope Proteins
  • G protein, vesicular stomatitis virus
  • Membrane Glycoproteins