Lentiviral Integration Preferences in Transgenic Mice

• Authors: Shang-Hsun Yang, Emory University; Pei-Hsun Cheng, Emory University; Robert T. Sullivan, Emory University; James W. Thomas, Emory University; Anthony Chan, Emory University
• Journal Title: genesis
• Volume: Volume 46, Number 12
• Publisher: Wiley: 12 months | 2008-12-01, Pages 711-718
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/dvg.20435
• Subjects: Biology, Genetics; Biology, Cell; Biology, Neuroscience
• Keywords: Science & Technology; Life Sciences & Biomedicine; Developmental Biology; Genetics & Heredity; lentiviral vector; transgenesis; integration; preference genome; mouse zygote; IMMUNODEFICIENCY-VIRUS TYPE-1; OVINE PULMONARY ADENOCARCINOMA; PSEUDOTYPED RETROVIRAL VECTORS; GENE-TRANSFER; HUMAN GENOME; CHROMOSOMAL POSITION; SITE SELECTION; HIGH-TITER; GERM LINE; IN-VITRO

Abstract

Lentiviral gene transfer has a significant impact on the development of biomedical research. One of the most important features of lentiviruses is the capability to infect both dividing and nondividing cells. However, little is known whether integration preference exists, specifically in early embryos. An in-depth genome analysis on 112 independent lentiviral integration sites from 43 transgenic founder mice was performed to determine if there are preferable sites for lentiviral integration in early embryonic genome. Our results demonstrated that lentiviruses were biased in integrating within intragenic regions, especially in the introns. However, no integration preference was found associated with specific chromosomes, repetitive elements, or CpG islands, nor was there any preference for integrating at close proximity to transcription start sites. Our findings suggested that lentiviruses were biased to integrate into the intragenic regions of early embryonic genome of mouse.