Amplicon Vectors as Outstanding Tools to Study and Modify Cognitive Functions

Abstract

This review summarizes recent data on the use of HSV-1-based amplicon vectors for in vivo gene delivery to the brains of rats and mice to study and modify behaviour. Here we describe studies that have focused on cognitive functions like learning and memory. In addition, the use of amplicons in other behavioural studies, like addiction, social interaction, anxiety and stress, will be briefly updated. Several remarkable findings have been achieved, thanks to the use of these very efficient and non-toxic naturally neurotropic vectors, most particularly the consistent observation that genetic manipulation of a rather limited number of neurons in restricted regions of the brain, could result in significant behavioural changes, a notion that is therefore emerging as a common unifying hypothesis, thanks to these works.

Region-Specific Genetic Alterations in the Aging Hippocampus: Implications For Cognitive Aging

“…Microarray analysis provides both the tools and the groundwork for the development of hypothesis-driven functional validation studies to confirm the roles of potential molecular pathways identified with genomic technology. To determine how these genes and pathways are co-regulated will require future research using various molecular biology and genetic approaches such as the use of transgenic technology (Havekes and Abel, 2009) and viral and non-viral gene targeting (Burger et al, 2005; Jerusalinsky and Epstein, 2006; Lundberg et al, 2008; Schubert et al, 2008; Southgate et al, 2008). …”

Progress and prospects: Biological properties and technological advances of herpes simplex virus type 1-based amplicon vectors

“…A large number of in vitro and in vivo studies using helper-free amplicons that cannot be described in this short review, have shown the outstanding potential of these vectors for gene therapy of neurological diseases, 26 Herpes simplex virus type 1-based vectors AL Epstein for the treatment of brain and other malignancies, 27 for fundamental studies of neurobiological 28 or virological 29 interest, and as genetic vector vaccines against pathogens. 30 Despite encouraging results, translation to large animal models is challenging and concern remains about clinical application, except perhaps for cancer treatment.…”

From neuroanatomy to gene therapy: searching for new ways to manipulate the supraspinal endogenous pain modulatory system

“…Based on the affinity of HSV‐1 to the neuron and the appearance of improved HSV‐based constructs, like amplicons (Jerusalinsky & Epstein , 2 006), this will still be a viral of choice in gene therapy for chronic pain. In order to use HSV‐1‐based gene therapy to target the endogenous pain modulatory system, it is important (1) to distinguish neurons involved in nociceptive processing from neurons participating in other brain functions, and (2) to ascertain how HSV‐1 constructs will migrate retrogradely upon local delivery.…”