Lentiviral vectors for immune cells targeting

Abstract

Lentiviral vectors are efficient gene delivery vehicles suitable for delivering long-term transgene expression in various cell types. Engineering lentiviral vectors to have the capacity to transduce specific cell types is of great interest to advance the translation of lentiviral vectors towards the clinic. Here we provide an overview of innovative approaches to target lentiviral vectors to cells of the immune system. In this overview we distinguish between two types of lentiviral vector targeting strategies: 1) targeting of the vectors to specific cells by lentiviral vector surface modifications, and 2) targeting at the level of transgene transcription by insertion of tissue-specific promoters to drive transgene expression. It is clear that each strategy is of enormous value but ultimately combining these approaches may help reduce the effects of off-target expression and improve the efficiency and saftey of lentiviral vectors for gene therapy.

Recombinant Viral Vectors for Investigating DNA Damage Responses and Gene Therapy of Xeroderma Pigmentosum

“…This enzyme transcribes the virus' RNA into a DNA sequence that the host cell machinery can transcribe and translate (Froelich et al, 2010).…”

“…Retroviral vectors are capable of transducing a wide range of cell types, are able to accommodate extensive changes in their genome, accept long transgenes, have low immunogenicity, can be produced in high titers, and promote a prolonged transgene expression due to their ability to integrate into the host cell genome (Froelich et al, 2010). On the other hand, most retroviral vectors can only transduce replicating cells since the transport of the transcribed viral DNA to the nucleus is mitosis-dependent.…”

“…On the other hand, most retroviral vectors can only transduce replicating cells since the transport of the transcribed viral DNA to the nucleus is mitosis-dependent. Additionally, there is always the risk of insertional mutagenesis due to the semi-random integration of the vector genome in the host cell's genome (Froelich et al, 2010). Nowadays, the most widely used retroviruses as gene therapy tools are the lentiviruses (LVs), such as the human immunodeficiency virus (HIV).…”

“…These vectors have the same advantages as other retroviral vectors and are capable of transducing post mitotic cells. Moreover, the LVs tend not to integrate by transcription initiation sites, reducing the risk of insertional tumorigenesis (Froelich et al, 2010). The retroviral vectors were the first vectors used in gene therapy clinical trials in 1989 (Edelstein et al, 2007, Rosenberg et al, 1990 and are extensively used in fundamental biological research, functional genomics and gene therapy (Mátrai et al, 2010).…”

Pseudotyping Lentiviral Vectors with Lymphocytic Choriomeningitis Virus Glycoproteins for Transduction of Dendritic Cells andIn VivoImmunization

“…These phenotypically mixed particles, or pseudotypes, are constructed by incorporating heterologous glycoproteins onto the LV surface through the budding process in the producing cells (Cronin et al, 2005). The most commonly used Env glycoprotein of pseudotyped LVs is derived from vesicular stomatitis virus (VSV-G), which mediates viral entry through the binding of membrane phospholipids (Froelich et al, 2010;Giacca and Zacchigna, 2012), and a recent study showed that LDL receptor serves as the cellular receptors for VSV-G-pseudotyped LVs (Finkelshtein et al, 2013). Although VSV-G-pseudotyped LVs have broadened the range of infected cell types and possess good stability (Froelich et al, 2010), they also have some disadvantages, including toxicity of constitutive expression in producer cell lines and the susceptibility of inactivation by human complement (Ory et al, 1996;DePolo et al, 2000).…”