Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for Sensitive Analysis of Residual Protein Tat Bh1-101 in Lentiviral Vectors for Gene Therapy

Hum Gene Ther. 2023 Nov;34(21-22):1162-1171. doi: 10.1089/hum.2023.030. Epub 2023 Oct 26.

Abstract

Lentiviral (LV) vector-based gene therapy is gaining popularity for treating a wide range of diseases. Various LV vectors are being developed for transducing cells in cellular gene therapy at St. Jude. Some LV vectors are produced using stable 293T packaging cell lines, which includes gag-pol-rev-tat and virus-glycoprotein. Transactivating factor (transactivator of transcription [Tat]) is a regulatory protein that drastically increases the efficiency of lentiviral transcription. Residual analysis of Tat is critical for gene vector quality and safety. In this work, we developed a highly sensitive liquid chromatography-tandem mass spectrometry method for analysis of residual Tat in Lentivirus as an alternative to enzyme-linked immunosorbent assay. Residual Tat in LV can be accurately quantified with high specificity with a limit of detection of 0.3 ng/mL.

Keywords: LC-MS/MS; lentiviral vectors; mass spectrometry; quantification; transactivator of transcription.

MeSH terms

  • Genetic Therapy
  • Genetic Vectors / genetics
  • Lentivirus / genetics
  • Tandem Mass Spectrometry*
  • Trans-Activators* / genetics
  • Transduction, Genetic

Substances

  • Trans-Activators