Integrase-deficient lentivirus: opportunities and challenges for human gene therapy.

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.

Cutl1: a potential target for cancer therapy.

CDP, a key transcription regulator encoded by Cutl1 gene, has been demonstrated to be involved in repressing or promoting expression of target genes through its specific DNA-binding, meanwhile, the activity of CDP was influenced by some types of modifications including transcriptional, posttranscriptional, translational and posttranslational modifications. In this review, we systematically analyzed the role of CDP in normal development and tumor progression, and then emphasized its interactors and downstream molecules. Eventually, we concluded that Cut1 could promote cancer progression and its down-regulating expression will be a promising strategy for cancer therapy.