Evaluating risks of insertional mutagenesis by DNA transposons in gene therapy

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

Research output: Contribution to journalReview article

60 Citations (Scopus)

Abstract

Investigational therapy can be successfully undertaken using viral- and nonviral-mediated ex vivo gene transfer. Indeed, recent clinical trials have established the potential for genetically modified T cells to improve and restore health. Recently, the Sleeping Beauty (SB) transposon/transposase system has been applied in clinical trials to stably insert a chimeric antigen receptor (CAR) to redirect T-cell specificity. We discuss the context in which the SB system can be harnessed for gene therapy and describe the human application of SB-modified CAR+ T cells. We have focused on theoretical issues relating to insertional mutagenesis in the context of human genomes that are naturally subjected to remobilization of transposons and the experimental evidence over the last decade of employing SB transposons for defining genes that induce cancer. These findings are put into the context of the use of SB transposons in the treatment of human disease.

Original languageEnglish (US)
Pages (from-to)265-283
Number of pages19
JournalTranslational Research
Volume161
Issue number4
DOIs
StatePublished - Apr 2013

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Beauty
Gene therapy
Mutagenesis
DNA Transposable Elements
T-cells
Insertional Mutagenesis
Genetic Therapy
Genes
Transposases
Gene transfer
Antigen Receptors
T-Cell Antigen Receptor
Health
Clinical Trials
T-Cell Antigen Receptor Specificity
Investigational Therapies
Neoplasm Genes
Human Genome
T-Lymphocytes

Cite this

Evaluating risks of insertional mutagenesis by DNA transposons in gene therapy. / Hackett, Perry B.; Largaespada, David A.; Switzer, Kirsten C.; Cooper, Laurence J.N.

In: Translational Research, Vol. 161, No. 4, 04.2013, p. 265-283.

Research output: Contribution to journalReview article

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