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This article is part of the supplement: Transposons in vertebrate functional genomics

Review

Predicting preferential DNA vector insertion sites: implications for functional genomics and gene therapy

Christopher S Hackett1, Aron M Geurts2 and Perry B Hackett3*

Author Affiliations

1 Biomedical Sciences Graduate Program and Department of Neurology, University of California San Francisco, Room U441K, Parnassus Ave, San Francisco, California 94143-0663, USA

2 Human and Molecular Genetics Center, Medical College of Wisconsin, Room HRC 5200, Watertown Plank Rd, Milwaukee, Wisconsin 53226, USA

3 Department of Genetics, Cell Biology, and Development, The Arnold and Mabel Beckman Center for Transposon Research, Gene Therapy Program, and Cancer Center, University of Minnesota, Room 6-160 Jackson Hall, Church St, Minneapolis, Minnesota 55455, USA

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Genome Biology 2007, 8(Suppl 1):S12  doi:10.1186/gb-2007-8-s1-s12

Published: 31 October 2007

Abstract

Viral and transposon vectors have been employed in gene therapy as well as functional genomics studies. However, the goals of gene therapy and functional genomics are entirely different; gene therapists hope to avoid altering endogenous gene expression (especially the activation of oncogenes), whereas geneticists do want to alter expression of chromosomal genes. The odds of either outcome depend on a vector's preference to integrate into genes or control regions, and these preferences vary between vectors. Here we discuss the relative strengths of DNA vectors over viral vectors, and review methods to overcome barriers to delivery inherent to DNA vectors. We also review the tendencies of several classes of retroviral and transposon vectors to target DNA sequences, genes, and genetic elements with respect to the balance between insertion preferences and oncogenic selection. Theoretically, knowing the variables that affect integration for various vectors will allow researchers to choose the vector with the most utility for their specific purposes. The three principle benefits from elucidating factors that affect preferences in integration are as follows: in gene therapy, it allows assessment of the overall risks for activating an oncogene or inactivating a tumor suppressor gene that could lead to severe adverse effects years after treatment; in genomic studies, it allows one to discern random from selected integration events; and in gene therapy as well as functional genomics, it facilitates design of vectors that are better targeted to specific sequences, which would be a significant advance in the art of transgenesis.