A stable producer cell line for the manufacture of a lentiviral vector for gene therapy of Parkinson's disease

HJ Stewart, LF Wong, IT Strickland, D Chipchase, M Kelleher, L Stevenson, V Thoree, J McCarthy, G Scott Ralph, KA Mitrophanous, PA Radcliffe

Research output: Contribution to journalArticle (Academic Journal)

16 Citations (Scopus)

Abstract

Abstract ProSavin is an equine infectious anemia virus vector-based gene therapy for Parkinson's disease for which inducible HEK293T-based producer cell lines (PCLs) have been developed. These cell lines demonstrate stringent tetracycline-regulated expression of the packaging components and yield titers comparable to the established transient production system. A prerequisite for the use of PCL-derived lentiviral vectors (LVs) in clinical applications is the thorough characterization of both the LV and respective PCL with regard to identity and genetic stability. We describe the detailed characterization of two ProSavin PCLs (PS5.8 and PS46.2) and resultant ProSavin vector. The two cell lines demonstrate stable production of vector over a time period sufficient to allow generation of master and working cell banks, and subsequent large-scale vector production. ProSavin generated from the PCLs performs comparably in vivo to that produced by the standard transient transfection process with respect to transduction efficiency and immunogenicity. The development of ProSavin PCLs, and the detailed characterization described here, will aid the advancement of ProSavin for clinical application.
Translated title of the contributionA stable producer cell line for the manufacture of a lentiviral vector for gene therapy of Parkinson's disease
Original languageEnglish
Pages (from-to)357 - 369
Number of pages12
JournalHuman Gene Therapy
Volume22(3)
DOIs
Publication statusPublished - Mar 2011

Fingerprint Dive into the research topics of 'A stable producer cell line for the manufacture of a lentiviral vector for gene therapy of Parkinson's disease'. Together they form a unique fingerprint.

  • Cite this

    Stewart, HJ., Wong, LF., Strickland, IT., Chipchase, D., Kelleher, M., Stevenson, L., Thoree, V., McCarthy, J., Scott Ralph, G., Mitrophanous, KA., & Radcliffe, PA. (2011). A stable producer cell line for the manufacture of a lentiviral vector for gene therapy of Parkinson's disease. Human Gene Therapy, 22(3), 357 - 369. https://doi.org/10.1089/hum.2010.142