Making lentiviral vectors more powerful and universal.
Extract: We recently published our work constructing lentiviral vectors (LV) to consistently express two genes simultaneously or independently. In a separate study, we reported efficient gene transfer to human T lymphocytes while retaining the T cell functionality and antigen repertoire. Recombinant vectors based on retroviruses (including both onco-retroviruses and lentiviruses) remain the only choice to efficiently and stably transduce primary mammalian cells. Compared to onco-retroviral vectors (RVs), which have been the mainstay for stable gene delivery in the past 20 years, LVs offer several advantages. First, LVs can transduce both dividing and non-dividing cells such as freshly isolated hematopoietic stem cells (HSCs) and T cells in blood. Second, LVs can accommodate the use of various transcriptional promoters, either ubiquitous or cell-specific. The self-inactivating (SIN) safety modification of LVs, which permanently disables the viral promoter within the viral long-terminal repeat (LTR) after integration, enables transgene expression in the targeted cells to be controlled solely by internal promoters. Importantly, SIN modification of LVs does not reduce viral titers, in sharp contrast to that of RVs.
Ye
Zhaohui
Z
Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Baltimore, MD 21231, USA.
Cheng
Linzhao
L