Abstract
Recent commercialization of lentiviral vector (LV)-based cell therapies and successful reports of clinical studies have demonstrated the untapped potential of LVs to treat diseases and benefit patients. LVs hold notable and inherent advantages over other gene transfer agents based on their ability to transduce non-dividing cells, permanently transform target cell genome, and allow stable, long-term transgene expression. LV systems based on non-human lentiviruses are attractive alternatives to conventional HIV-1-based LVs due to their lack of pathogenicity in humans. This article reviews non-human lentiviruses and highlights their unique characteristics regarding virology and molecular biology. The LV systems developed based on these lentiviruses, as well as their successes and shortcomings, are also discussed. As the field of gene therapy is advancing rapidly, the use of LVs uncovers further challenges and possibilities. Advances in virology and an improved understanding of lentiviral biology will aid in the creation of recombinant viral vector variants suitable for translational applications from a variety of lentiviruses.
Highlights
Introduction to Lentiviral VectorsThe field of gene and cell therapy is advancing rapidly with lentiviral-based vectors being the preferred vector of choice due to their ability to infect both dividing and non-dividing cells and integrate transgenes into the host cell genome [1]
S2 vpw vpy tmx Another trademark feature of non-primate lentiviruses is the deoxyuridine triphosphate nucleotidohydrolase enzyme, which is not encoded by HIV or simian immunodeficiency virus (SIV)
A substantial amount of research has been performed to understand the molecular biology of the lentiviral life cycle due to its advantageous characteristics: relatively large packaging capacity, ability to infect non-dividing cells, allowing for stable transgene expression, and low immunogenicity
Summary
The field of gene and cell therapy is advancing rapidly with lentiviral-based vectors being the preferred vector of choice due to their ability to infect both dividing and non-dividing cells and integrate transgenes into the host cell genome [1]. Lentiviruses belong to the Orthoretroviridae subfamily of the genus retroviruses and are characterized by their long latent incubation periods with low levels of viral pathogenicity [2]. They are divided into two major classes: primate and non-primate lentiviruses [3]. The primate lentiviruses include human immunodeficiency virus type 1 (HIV-1) and 2 (HIV-2) and simian immunodeficiency virus (SIV). The HIV-1 pandemic in the twentieth century and the resulting acquired immune deficiency syndrome (AIDS) instigated extensive research into the virus and uncovered crucial information regarding viral genome organization, replication, and life cycle, paving the way for the generation of HIV-1-based lentiviral vectors (LVs). Other members include feline immunodeficiency virus (FIV) [5,6], equine infectious anemia virus (EIAV) [7], caprine arthritis encephalitis virus (CAEV) [8], bovine immunodeficiency virus (BIV) [9], and jembrana disease virus (JDV) [10]
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