Risks of Insertional Mutagenesis by DNA Transposons in Cancer Gene Therapy

Perry B. Hackett, Timothy K. Starr, Laurence J.N. Cooper

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Citations (Scopus)

Abstract

The Sleeping Beauty (SB) transposon/transposase system has recently been applied in clinical trials to redirect T-cell specificity through the addition of a transgenic cassette that drives expression of a chimeric antigen receptor. This chapter focuses on issues relating to insertional mutagenesis in the context of the plasticity of human genomes; the unexpected variability in human genomes elucidated by recent high-throughput, whole-genome sequencing; and the recently discovered high rates of remobilization of endogenous transposable elements. These findings are discussed in the context of using SB transposons to treat human disease and suggest that integration by SB transposons is not likely to induce adverse events in the clinic.

Original languageEnglish (US)
Title of host publicationTranslating Gene Therapy to the Clinic
Subtitle of host publicationTechniques and Approaches
PublisherElsevier Inc.
Pages65-83
Number of pages19
ISBN (Electronic)9780128005644
ISBN (Print)9780128005637
DOIs
StatePublished - Jan 1 2015

Fingerprint

Beauty
Gene therapy
Mutagenesis
DNA Transposable Elements
Insertional Mutagenesis
Neoplasm Genes
Genetic Therapy
Genes
Human Genome
T-Cell Antigen Receptor Specificity
Transposases
Antigen Receptors
T-cells
Plasticity
Throughput
Clinical Trials
Genome

Keywords

  • AAPC, Artificial antigen-presenting cell
  • CAR, Chimeric antigen receptor
  • HSC, Hematopoietic stem cell
  • ITR, Inverted terminal repeat
  • LINE/SINE, Long/short interspersed elements
  • SB, Sleeping Beauty

Cite this

Hackett, P. B., Starr, T. K., & Cooper, L. J. N. (2015). Risks of Insertional Mutagenesis by DNA Transposons in Cancer Gene Therapy. In Translating Gene Therapy to the Clinic: Techniques and Approaches (pp. 65-83). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-800563-7.00005-1

Risks of Insertional Mutagenesis by DNA Transposons in Cancer Gene Therapy. / Hackett, Perry B.; Starr, Timothy K.; Cooper, Laurence J.N.

Translating Gene Therapy to the Clinic: Techniques and Approaches. Elsevier Inc., 2015. p. 65-83.

Research output: Chapter in Book/Report/Conference proceedingChapter

Hackett, PB, Starr, TK & Cooper, LJN 2015, Risks of Insertional Mutagenesis by DNA Transposons in Cancer Gene Therapy. in Translating Gene Therapy to the Clinic: Techniques and Approaches. Elsevier Inc., pp. 65-83. https://doi.org/10.1016/B978-0-12-800563-7.00005-1
Hackett PB, Starr TK, Cooper LJN. Risks of Insertional Mutagenesis by DNA Transposons in Cancer Gene Therapy. In Translating Gene Therapy to the Clinic: Techniques and Approaches. Elsevier Inc. 2015. p. 65-83 https://doi.org/10.1016/B978-0-12-800563-7.00005-1
Hackett, Perry B. ; Starr, Timothy K. ; Cooper, Laurence J.N. / Risks of Insertional Mutagenesis by DNA Transposons in Cancer Gene Therapy. Translating Gene Therapy to the Clinic: Techniques and Approaches. Elsevier Inc., 2015. pp. 65-83
@inbook{9161d1b60a034e4592fff768652d9824,
title = "Risks of Insertional Mutagenesis by DNA Transposons in Cancer Gene Therapy",
abstract = "The Sleeping Beauty (SB) transposon/transposase system has recently been applied in clinical trials to redirect T-cell specificity through the addition of a transgenic cassette that drives expression of a chimeric antigen receptor. This chapter focuses on issues relating to insertional mutagenesis in the context of the plasticity of human genomes; the unexpected variability in human genomes elucidated by recent high-throughput, whole-genome sequencing; and the recently discovered high rates of remobilization of endogenous transposable elements. These findings are discussed in the context of using SB transposons to treat human disease and suggest that integration by SB transposons is not likely to induce adverse events in the clinic.",
keywords = "AAPC, Artificial antigen-presenting cell, CAR, Chimeric antigen receptor, HSC, Hematopoietic stem cell, ITR, Inverted terminal repeat, LINE/SINE, Long/short interspersed elements, SB, Sleeping Beauty",
author = "Hackett, {Perry B.} and Starr, {Timothy K.} and Cooper, {Laurence J.N.}",
year = "2015",
month = "1",
day = "1",
doi = "10.1016/B978-0-12-800563-7.00005-1",
language = "English (US)",
isbn = "9780128005637",
pages = "65--83",
booktitle = "Translating Gene Therapy to the Clinic",
publisher = "Elsevier Inc.",

}

TY - CHAP

T1 - Risks of Insertional Mutagenesis by DNA Transposons in Cancer Gene Therapy

AU - Hackett, Perry B.

AU - Starr, Timothy K.

AU - Cooper, Laurence J.N.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - The Sleeping Beauty (SB) transposon/transposase system has recently been applied in clinical trials to redirect T-cell specificity through the addition of a transgenic cassette that drives expression of a chimeric antigen receptor. This chapter focuses on issues relating to insertional mutagenesis in the context of the plasticity of human genomes; the unexpected variability in human genomes elucidated by recent high-throughput, whole-genome sequencing; and the recently discovered high rates of remobilization of endogenous transposable elements. These findings are discussed in the context of using SB transposons to treat human disease and suggest that integration by SB transposons is not likely to induce adverse events in the clinic.

AB - The Sleeping Beauty (SB) transposon/transposase system has recently been applied in clinical trials to redirect T-cell specificity through the addition of a transgenic cassette that drives expression of a chimeric antigen receptor. This chapter focuses on issues relating to insertional mutagenesis in the context of the plasticity of human genomes; the unexpected variability in human genomes elucidated by recent high-throughput, whole-genome sequencing; and the recently discovered high rates of remobilization of endogenous transposable elements. These findings are discussed in the context of using SB transposons to treat human disease and suggest that integration by SB transposons is not likely to induce adverse events in the clinic.

KW - AAPC, Artificial antigen-presenting cell

KW - CAR, Chimeric antigen receptor

KW - HSC, Hematopoietic stem cell

KW - ITR, Inverted terminal repeat

KW - LINE/SINE, Long/short interspersed elements

KW - SB, Sleeping Beauty

UR - http://www.scopus.com/inward/record.url?scp=84944385381&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84944385381&partnerID=8YFLogxK

U2 - 10.1016/B978-0-12-800563-7.00005-1

DO - 10.1016/B978-0-12-800563-7.00005-1

M3 - Chapter

AN - SCOPUS:84944385381

SN - 9780128005637

SP - 65

EP - 83

BT - Translating Gene Therapy to the Clinic

PB - Elsevier Inc.

ER -