Integrase-Deficient Lentivirus: Opportunities and Challenges for Human Gene Therapy

Title:Integrase-Deficient Lentivirus: Opportunities and Challenges for Human Gene Therapy

Volume: 14 Issue: 5

Author(s): Kuan-Can Liu, Bao-Shun Lin, An-Ding Gao, Hong-Yu Ma, Meng Zhao, Rui Zhang, Hui-Hui Yan, Xun-Fei Yi, Si-Jie Lin, Jian-Wen Que and Xiao-Peng Lan

Affiliation:

Keywords: Gene delivery, gene therapy, genome manipulation, integrase-deficient lentivirus, non-integrating lentiviral vectors.

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.

Cite this article as:

Liu Kuan-Can, Lin Bao-Shun, Gao An-Ding, Ma Hong-Yu, Zhao Meng, Zhang Rui, Yan Hui-Hui, Yi Xun-Fei, Lin Si-Jie, Que Jian-Wen and Lan Xiao-Peng, Integrase-Deficient Lentivirus: Opportunities and Challenges for Human Gene Therapy, Current Gene Therapy 2014; 14 (5) . https://dx.doi.org/10.2174/1566523214666140825124311