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Targeted gene insertion for molecular medicine

Item Type:Review
Title:Targeted gene insertion for molecular medicine
Creators Name:Voigt, K. and Izsvak, Z. and Ivics, Z.
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, Animals
Source:Journal of Molecular Medicine
ISSN:0946-2716
Publisher:Springer (Germany)
Volume:86
Number:11
Page Range:1205-1219
Date:November 2008
Additional Information:The original publication is available at www.springerlink.com
Official Publication:https://doi.org/10.1007/s00109-008-0381-8
PubMed:View item in PubMed

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