Rapid and Efficient Stable Gene Transfer to Mesenchymal Stromal Cells Using a Modified Foamy Virus Vector

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Nathan Paul Sweeney - , Imperial College London (Author)
  • Cathy Regan - , Western University (Author)
  • Jiahui Liu - , Western University (Author)
  • Antonio Galleu - , King's College London (KCL) (Author)
  • Francesco Dazzi - , King's College London (KCL) (Author)
  • Dirk Lindemann - , Institute of Medical Microbiology and Virology, Center for Regenerative Therapies Dresden (Author)
  • Charles Anthony Rupar - , Western University (Author)
  • Myra Olga McClure - , Imperial College London (Author)

Abstract

Mesenchymal stromal cells (MSCs) hold great promise for regenerative medicine. Stable ex vivo gene transfer to MSCs could improve the outcome and scope of MSC therapy, but current vectors require multiple rounds of transduction, involve genotoxic viral promoters and/or the addition of cytotoxic cationic polymers in order to achieve efficient transduction. We describe a self-inactivating foamy virus vector (FVV), incorporating the simian macaque foamy virus envelope and using physiological promoters, which efficiently transduces murine MSCs (mMSCs) in a single-round. High and sustained expression of the transgene, whether GFP or the lysosomal enzyme, arylsulphatase A (ARSA), was achieved. Defining MSC characteristics (surface marker expression and differentiation potential), as well as long-term engraftment and distribution in the murine brain following intracerebroventricular delivery, are unaffected by FVV transduction. Similarly, greater than 95% of human MSCs (hMSCs) were stably transduced using the same vector, facilitating human application. This work describes the best stable gene transfer vector available for mMSCs and hMSCs.

Details

Original languageEnglish
Pages (from-to)1227-36
Number of pages10
JournalMolecular Therapy
Volume24
Issue number7
Publication statusPublished - Aug 2016
Peer-reviewedYes

External IDs

PubMedCentral PMC4982542
ORCID /0000-0002-0320-4223/work/150885011
Scopus 84976271848

Keywords

Keywords

  • Animals, Cell Line, Gene Expression, Gene Order, Gene Transfer Techniques, Genetic Vectors/genetics, Humans, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells/metabolism, Mice, Promoter Regions, Genetic, Spumavirus/genetics, Transduction, Genetic, Transgenes