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

Content Provider	Springer Nature : BioMed Central
Author	Hackett, Christopher S Geurts, Aron M Hackett, Perry B
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.
Related Links	https://genomebiology.biomedcentral.com/counter/pdf/10.1186/gb-2007-8-s1-s12.pdf
Ending Page	17
Page Count	17
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/gb-2007-8-s1-s12
Journal	Genome Biology
Issue Number	1
Volume Number	8
Language	English
Publisher	BioMed Central
Publisher Date	2007-10-31
Access Restriction	Open
Subject Keyword	Animal Genetics and Genomics Human Genetics Plant Genetics and Genomics Microbial Genetics and Genomics Bioinformatics Evolutionary Biology Gene Therapy Sleep Beauty Gene Therapy Vector Sleep Beauty Transposase Common Integration Site
Content Type	Text
Resource Type	Review
Subject	Biotechnology Genetics
Journal Impact Factor	10.1/2023
5-Year Journal Impact Factor	16.5/2023

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