Abstract
The stable introduction of therapeutic transgenes into human cells can be accomplished using viral and nonviral approaches. Transduction with clinical-grade recombinant viruses offers the potential of efficient gene transfer into primary cells and has a record of therapeutic successes. However, widespread application for gene therapy using viruses can be limited by their initially high cost of manufacture at a limited number of production facilities as well as a propensity for nonrandom patterns of integration. The ex vivo application of transposon-mediated gene transfer now offers an alternative to the use of viral vectors. Clinical-grade DNA plasmids can be prepared at much reduced cost and with lower immunogenicity, and the integration efficiency can be improved by the transient coexpression of a hyperactive transposase. This has facilitated the design of human trials using the Sleeping Beauty (SB) transposon system to introduce a chimeric antigen receptor (CAR) to redirect the specificity of human T cells. This review examines the rationale and safety implications of application of the SB system to genetically modify T cells to be manufactured in compliance with current good manufacturing practice (cGMP) for phase I/II trials.
Original language | English (US) |
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Pages (from-to) | 674-683 |
Number of pages | 10 |
Journal | Molecular Therapy |
Volume | 18 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2010 |
Bibliographical note
Funding Information:We thank Elena L. Aronovich for helpful discussions. This project was supported by NIH grants P01HD32652 and R01DK082516 to P.B.H., R01CA113636 to D.A.L., and RO1CA124782 and R01CA120956 to L.J.N.C.