Prospects and implications of using chromatin insulators in gene therapy and transgenesis
Open Access
- 21 June 2004
- Vol. 26 (7) , 796-807
- https://doi.org/10.1002/bies.20059
Abstract
Gene therapy has emerged from the idea of inserting a wild‐type copy of a gene in order to restore the proper expression and function of a damaged gene. Initial efforts have focused on finding the proper vector and delivery method to introduce a corrected gene to the affected tissue or cell type. Even though these first attempts are clearly promising, seveal problems remain unsolved. A major problem is the influence of chromatin structure on transgene expression. To overcome chromatin‐dependent repressive transgenic states, researchers have begun to use chromatin regulatory elements to drive transgene expression. Insulators or chromatin boundaries are able to protect a transgene against chromatin position effects at their genomic integration sites, and they are able to maintain transgene expression for long periods of time. Therefore, these elements may be very useful tools in gene therapy applications for ensuring high‐level and stable expression of transgenes. BioEssays 26:796–807, 2004.Keywords
This publication has 77 references indexed in Scilit:
- Lentivirus Vectors Incorporating the Immunoglobulin Heavy Chain Enhancer and Matrix Attachment Regions Provide Position-Independent Expression in B LymphocytesJournal of Virology, 2003
- Progress and problems with the use of viral vectors for gene therapyNature Reviews Genetics, 2003
- Development of virus vectors for gene therapy of β chain hemoglobinopathies: flanking with a chromatin insulator reduces γ-globin gene silencing in vivoBlood, 2002
- The barrier function of an insulator couples high histone acetylation levels with specific protection of promoter DNA from methylationGenes & Development, 2002
- beta-globin YAC transgenes exhibit uniform expression levels but position effect variegation in miceHuman Molecular Genetics, 2000
- Use of matrix attachment regions (MARs) to minimize transgene silencingPlant Molecular Biology, 2000
- Development of a Condensed Locus Control Region Cassette and Testing in Retrovirus Vectors forAγ-GlobinBlood Cells, Molecules, and Diseases, 1998
- Locus Control Region Function and Heterochromatin-Induced Position Effect VariegationScience, 1996
- Generation of a high-titer retroviral vector capable of expressing high levels of the human beta-globin gene.Proceedings of the National Academy of Sciences, 1995
- Position-independent, high-level expression of the human β-globin gene in transgenic miceCell, 1987