CMV-GCaMP6f Lentivirus

With the first approval of AAV1 vectors in Europe for the treatment of lipoprotein lipase deficiency, gene therapy based on viral vectors is rapidly developing into routine treatment for rare and acquired diseases, for which different viral vector systems are available. Depending on the therapeutic goal and the target cells or tissues to be treated, the choice of one or another vector system is preferred. In the case of cell division, integrating vectors are required to achieve long-term expression of the transgene. Traditionally, retroviral vectors (in the broad sense) have been the vectors of choice because of their ability to stably integrate the transgene to be expressed. Two different retroviral vector systems have been developed: gammaretroviral vectors derived from murine leukemia virus (MLV) and lentiviral vectors (LV), mainly derived from HIV-1. In the past, many clinical trials based on MLV vectors have been successful, and although these vectors are still in use, the general trend is to use LV vectors. There are many reasons for this shift: (i) lentiviral vectors are able to transduce non-dividing cells across the nuclear membrane, compared to γ-retroviral vectors; (ii) their integration pattern is different from that of pluripotent viral vectors (MLVs), and the risk of insertional mutagenesis appears to be lower; and (iii) they can be produced at high vector titers. Lentiviral vectors have been successfully used in clinical trials, first for the treatment of rare diseases, particularly primary immunodeficiencies and neurodegenerative storage diseases. However, their use in the treatment of more common inherited and acquired diseases, including β-thalassemia, Parkinson's disease, and chimeric antigen receptor-based cancer immunotherapy, has been evaluated in the clinic with promising results.