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Gene therapy vectors: the prospects and potentials of the cut-and-paste transposons

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Abstract

Gene therapy applications require efficient tools for the stable delivery of genetic information into eukaryotic genomes. Most current gene delivery strategies are based on viral vectors. However, a number of drawbacks, such as the limited cargo capacity, host immune response and mutational risks, highlight the need for alternative gene delivery tools. A comprehensive gene therapy tool kit should contain a range of vectors and techniques that can be adapted to different targets and purposes. Transposons provide a potentially powerful approach. However, transposons encompass a large number of different molecular mechanisms, some of which are better suited to gene delivery applications than others. Here, we consider the range and potentials of the various mechanisms, focusing on the cut-and-paste transposons as one of the more promising avenues towards gene therapy applications. Several cut-and-paste transposition systems are currently under development. We will first consider the mechanisms of piggyBac and the hAT family elements Tol1 and Tol2, before focusing on the mariner family elements including Mos1, Himar1 and Hsmar1.

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Abbreviations

cDNA:

Complementary DNA

EMSA:

Electrophoretic mobility shift assay

HTH:

Helix-turn-helix

IR:

Inverted repeat

kb:

Kilobase

LTR:

Long-terminal-repeat

NLS:

Nuclear localization signal

OPI:

Over-production inhibition

PEC:

Paired-end complex

Rep:

Replication

RSS:

Recombination signal sequences

RT:

Reverse-transcription

SEC:

Single-end complex

Tnp:

Transposon

TP:

Target-primed

Txn:

Transcription

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Acknowledgments

Work in the author’s laboratory is funded by The European Commission (Project SyntheGene Delivery, No. 018716) and the Wellcome Trust. We would like to thank Dr. Yves Bigot for his help and his enthusiastic inspiration throughout this work.

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  1. School of Biomedical Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham, NG7 2UH, UK

    Corentin Claeys Bouuaert & Ronald M. Chalmers

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Correspondence to Ronald M. Chalmers.

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Claeys Bouuaert, C., Chalmers, R.M. Gene therapy vectors: the prospects and potentials of the cut-and-paste transposons. Genetica 138, 473–484 (2010). https://doi.org/10.1007/s10709-009-9391-x

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