title: Integrase-deficient lentivirus: opportunities and challenges for human gene therapy.
abstract: Lentiviruses are powerful tools for gene delivery and have been widely used for the dissection of gene functions in both replicating and quiescent cells. Recently, lentiviruses have also been used for delivering target sequences in gene therapy. Although the lentiviral system provides sustained exogenous gene expression, serious concerns have been raised due to its unfavorable insertion-mediated mutagenesis effect, thereby resulting in the silencing or activation of some unexpected genes. Thus, an array of modifications of the original vectors may reduce risks. Here, we briefly review the structure of the integrase protein, which is an essential protein for viral insertion and integration; the mechanisms of integrase-mediated integration; and the effects of the modifications of integrase. Moreover, we discuss the advantages resulting from integrase modifications and their future applications. Taken together, the generation of integrase-deficient lentivirus (IDLV) not only provides us with an opportunity to reduce the risk of virus-mediated insertions, which would improve the safety of gene therapy, but also favors gene correction and vaccine development.
authors.forename: Kuan-Can
authors.initials: KC
authors.lastname: Liu
authors.forename: Bao-Shun
authors.initials: BS
authors.lastname: Lin
authors.forename: An-Ding
authors.initials: AD
authors.lastname: Gao
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Ma
authors.forename: Meng
authors.initials: M
authors.lastname: Zhao
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Yan
authors.forename: Xun-Fei
authors.initials: XF
authors.lastname: Yi
authors.forename: Si-Jie
authors.initials: SJ
authors.lastname: Lin
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Que
authors.affiliation: Institute for Laboratory Medicine, Fuzhou General Hospital, PLA, Fuzhou, Fujian, PR China. Lanxp@sina.com.
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Lan
mesh_terms: D000595:Amino Acid Sequence; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use*; D006801:Humans; D019426:Integrases / Q000172:deficiency* / Q000235:genetics; D016086:Lentivirus / Q000235:genetics*; D008969:Molecular Sequence Data
chemical_list: D019426:Integrases