A transposon and transposase system for human application

Perry B Hackett, David A Largaespada, Laurence J.N. Cooper

Research output: Contribution to journalReview article

151 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)674-683
Number of pages10
JournalMolecular Therapy
Volume18
Issue number4
DOIs
StatePublished - Apr 1 2010

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Transposases
Beauty
T-Cell Antigen Receptor Specificity
Viruses
Costs and Cost Analysis
Antigen Receptors
Transgenes
Genetic Therapy
Genes
Plasmids
T-Lymphocytes
Safety
DNA
Therapeutics

Cite this

A transposon and transposase system for human application. / Hackett, Perry B; Largaespada, David A; Cooper, Laurence J.N.

In: Molecular Therapy, Vol. 18, No. 4, 01.04.2010, p. 674-683.

Research output: Contribution to journalReview article

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