Lentiviral vectors as tools to understand central nervous system biology in mammalian model organisms

Abstract

Lentiviruses have been extensively used as gene delivery vectors since the mid-1990s. Usually derived from the human immunodeficiency virus genome, they mediate efficient gene transfer to non-dividing cells, including neurons and glia in the adult mammalian brain. In addition, integration of the recombinant lentiviral construct into the host genome provides permanent expression, including the progeny of dividing neural precursors. In this review, we describe targeted vectors with modified envelope glycoproteins and expression of transgenes under the regulation of cell-selective and inducible promoters. This technology has broad utility to address fundamental questions in neuroscience and we outline how this has been used in rodents and primates. Combining viral tract tracing with immunohistochemistry and confocal or electron microscopy, lentiviral vectors provide a tool to selectively label and trace specific neuronal populations at gross or ultrastructural levels. Additionally, new generation optogenetic technologies can be readily utilized to analyze neuronal circuit and gene functions in the mature mammalian brain. Examples of these applications, limitations of current systems and prospects for future developments to enhance neuroscience knowledge will be reviewed. Finally, we will discuss how these vectors may be translated from gene therapy trials into the clinical setting.

Optogenetic stimulation: Understanding memory and treating deficits

“…The viral vector that is infused in a given brain location to enable optogenetic stimulation typically involves either a lentivirus (LV) or adeno‐associated virus (AAV), which have different properties with associated advantages and disadvantages for future clinical applications. LV has a relatively large particle size (100 nm), which restricts its diffusion through neural tissue (Parr‐Brownlie et al, ). This property of LVs is useful when the aim is to transduce neurons in a small nucleus.…”

Optogenetic approaches for dissecting neuromodulation and GPCR signaling in neural circuits

“…Lentiviruses have larger packaging capabilities, permitting the use of transcriptional promoters to target expression neuronal types, an approach not available with AAVs [125]. Cell-type specific promoters however may not a drive sufficient amount of expression [126].…”

Silencing of Peroxiredoxin-4 in Anticancer Activity of Gamma-Tocotrienol

“…However, it depends on the size and growth rate of the cell. This confluence is to ensure that the cells have enough space to divide during transduction, which takes about 96 h. A previous study showed that cell confluence of more than 50% limits the interaction of lentivirus, cells, and DNA complex [39]. On the other hand, cell confluence of less than 30% will slow down cell growth [40].…”