Shifting Retroviral Vector Integrations Away from Transcriptional Start Sites via DNA-Binding Protein Domain Insertion into Integraseopen access
- Authors
- Nam, Jung-soo; Lee, Ji-eun; Lee, Kwang-hee; Yang, Yeji; Kim, Soo-hyun; Bae, Gyu-un; Noh, Hohsuk; Lim, Kwang-il
- Issue Date
- Mar-2019
- Publisher
- CELL PRESS
- Keywords
- DNA-binding protein domain; gammaretroviral vectors; integrase; primer-binding site; transcriptional start sites
- Citation
- MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT, v.12, pp 58 - 70
- Pages
- 13
- Journal Title
- MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
- Volume
- 12
- Start Page
- 58
- End Page
- 70
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/3765
- DOI
- 10.1016/j.omtm.2018.11.001
- ISSN
- 2329-0501
2329-0501
- Abstract
- The unique ability of retroviruses to integrate genes into host genomes is of great value for long-term expression in gene therapy, but only when integrations occur at safe genomic sites. To reap the benefit of using retroviruses without severe detrimental effects, we developed several murine leukemia virus (MLV)-based gammaretroviral vectors with safer integration patterns by perturbing the structure of the integrase via insertion of DNA-binding zinc-finger domains (ZFDs) into an internal position of the enzyme. ZFD insertion significantly reduced the inherent, strong MLV integration preference for genomic regions near transcriptional start sites (TSSs), which are the most dangerous spots. The altered retroviral integration pattern was related to increased formation of residual primer-binding site sequences at the 3' end of proviruses. Several ZFD insertion mutants showed lower frequencies of integrations into the TSS genome regions when having the residual primer-binding site sequences in the proviruses. Our findings not only can extend the use of retroviruses in biomedical applications, but also provide a glimpse into the mechanisms underlying retroviral integration.
- Files in This Item
-
Go to Link
- Appears in
Collections - 공과대학 > 화공생명공학부 > 1. Journal Articles
- 이과대학 > 통계학과 > 1. Journal Articles
- 약학대학 > 약학부 > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.