Predicting preferential DNA vector insertion sites implications for functional genomics and gene therapy 英文参考文献.docVIP

Review Predicting preferential DNA vector insertion sites: implications for functional genomics and gene therapy Christopher S Hackett*, Aron M Geurts? and Perry B Hackett? *Biomedical Sciences Graduate Program and Department of Neurology, University of California San Francisco, Room U441K, Parnassus Ave, San Francisco, California 94143-0663, USA. ?Human and Molecular Genetics Center, Medical College of Wisconsin, Room HRC 5200, Watertown Plank Rd, Milwaukee, Wisconsin 53226, USA. ?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. Correspondence: Perry B Hackett. E-mail: perryh@ Published: 31 October 2007 Genome Biology 2007, 8(Suppl 1):S12 (doi:10.1186/gb-2007-8-S1-S12) The electronic version of this article is the complete one and can be found online at /2007/8/S1/S12 ? 2007 BioMed Central Ltd 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,