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Journal of Molecular Medicine

, Volume 86, Issue 11, pp 1205–1219 | Cite as

Targeted gene insertion for molecular medicine

  • Katrin Voigt
  • Zsuzsanna Izsvák
  • Zoltán Ivics
Review

Abstract

Genomic insertion of a functional gene together with suitable transcriptional regulatory elements is often required for long-term therapeutical benefit in gene therapy for several genetic diseases. A variety of integrating vectors for gene delivery exist. Some of them exhibit random genomic integration, whereas others have integration preferences based on attributes of the targeted site, such as primary DNA sequence and physical structure of the DNA, or through tethering to certain DNA sequences by host-encoded cellular factors. Uncontrolled genomic insertion bears the risk of the transgene being silenced due to chromosomal position effects, and can lead to genotoxic effects due to mutagenesis of cellular genes. None of the vector systems currently used in either preclinical experiments or clinical trials displays sufficient preferences for target DNA sequences that would ensure appropriate and reliable expression of the transgene and simultaneously prevent hazardous side effects. We review in this paper the advantages and disadvantages of both viral and non-viral gene delivery technologies, discuss mechanisms of target site selection of integrating genetic elements (viruses and transposons), and suggest distinct molecular strategies for targeted gene delivery.

Keywords

DNA-binding Zinc finger Transposon Virus Non-viral vectors Recombinase 

Notes

Acknowledgements

Work in the authors’ laboratory is supported by EU FP6 grant INTHER LSHB-CT-2005018961, and a grant from the Deutsche Forschungsgemeinschaft SPP1230 “Mechanisms of gene vector entry and persistence”.

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Katrin Voigt
    • 1
  • Zsuzsanna Izsvák
    • 1
    • 2
  • Zoltán Ivics
    • 1
  1. 1.Max Delbrück Center for Molecular MedicineBerlinGermany
  2. 2.Institute of BiochemistryBiological Research Center of the Hungarian Academy of SciencesSzegedHungary

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