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Predicting preferential DNA vector insertion sites: implications for functional genomics and gene therapy. Genome Biol 2007;8 Suppl 1:S12

Date

12/06/2007

Pubmed ID

18047689

Pubmed Central ID

PMC2106846

DOI

10.1186/gb-2007-8-s1-s12

Scopus ID

2-s2.0-38449089316   49 Citations

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.

Author List

Hackett CS, Geurts AM, Hackett PB

Author

Aron Geurts PhD Associate Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
DNA
Genetic Therapy
Genetic Vectors
Genome
Genomics
Humans
Mutagenesis, Insertional
jenkins-FCD Prod-406 0f9a74600e4e79798f8fa6f545ea115f3dd948b2