Lentiviral Vectors as Tools for the Study and Treatment of Glioblastoma

Abstract

Glioblastoma (GBM) has the worst prognosis among brain tumors, hence basic biology, preclinical, and clinical studies are necessary to design effective strategies to defeat this disease. Gene transfer vectors derived from the most-studied lentivirus—the Human Immunodeficiency Virus type 1—have wide application in dissecting GBM specific features to identify potential therapeutic targets. Last-generation lentiviruses (LV), highly improved in safety profile and gene transfer capacity, are also largely employed as delivery systems of therapeutic molecules to be employed in gene therapy (GT) approaches. LV were initially used in GT protocols aimed at the expression of suicide factors to induce GBM cell death. Subsequently, LV were adopted to either express small noncoding RNAs to affect different aspects of GBM biology or to overcome the resistance to both chemo- and radiotherapy that easily develop in this tumor after initial therapy. Newer frontiers include adoption of LV for engineering T cells to express chimeric antigen receptors recognizing specific GBM antigens, or for transducing specific cell types that, due to their biological properties, can function as carriers of therapeutic molecules to the cancer mass. Finally, LV allow the setting up of improved animal models crucial for the validation of GBM specific therapies.

The Dual Role of AQP4 in Cytotoxic and Vasogenic Edema Following Spinal Cord Contusion and Its Possible Association With Energy Metabolism via COX5A

“…To our knowledge, it is difficult to directly knock down targeted genes in vivo with high selectivity and specificity. As a post-transcriptional gene silencing mechanism, RNA interference (RNAi) can be used in certain biological systems to interfere with the expression of endogenous genes (Nellen and Lichtenstein, 1993; Escors and Breckpot, 2010; High et al, 2014), which demonstrates great promise for the study of signal transduction research, human gene function, and gene therapy (Fire et al, 1998; Del Vecchio et al, 2019). Meanwhile, the lentivirus can stably integrate itself into the host’s genome and its remarkable packaging capacity also renders it available to gene transfer tools (Morris, 2006; Pluta and Kacprzak, 2009).…”

Small interfering RNA target for long noncoding RNA PCGEM1 increases the sensitivity of LNCaP cells to baicalein

“…HIV‐1 lentiviral vector particles carrying target genes not only retain efficient infection and integration but also avoid damage to host cells in which viruses replicate. Moreover, the lentiviral vector carries green fluorescence, which is convenient for observing whether the target genes are transfected into the cell line (Del Vecchio, Calistri, Parolin, & Mucignat‐Caretta, 2019). New viral particles generated by host cells are not used to obtain the cell line stably expressing lentivirus.…”

Current Approaches for Glioma Gene Therapy and Virotherapy

“…Lentiviruses are single stranded positive sense RNA viruses that have been widely evaluated for the treatment of GBM (Del Vecchio et al, 2019 ). They are similar to RV but exhibit several advantages, mostly because lentiviral vectors (LV) integrate into the host genome but are less prone to insertional mutagenesis.…”

“…Third generation HIV-based vectors have been developed with higher transduction efficiency and safety. These vectors may be modified in order to achieve tissue tropism by pseudotyping and exhibit low immunogenicity due to the lack of viral protein expression (Del Vecchio et al, 2019 ). Lymphocytic choriomeningitis virus-pseudotyped LV were developed to achieve higher transduction efficiency in GBM cells, including glioma stem cells, in relation to normal brain cells (Miletic et al, 2004 ; Huszthy et al, 2009 ).…”