Abstract
Lentiviral vectors have been developed and used in multiple gene and cell therapy applications. One of their main advantages over other vectors is the ability to integrate the genetic material into the genome of the host. However, this can also be a disadvantage as it may lead to insertional mutagenesis. To address this, non-integrating lentiviral vectors (NILVs) were developed. To generate NILVs, it is possible to introduce mutations in the viral enzyme integrase and/or mutations on the viral DNA recognised by integrase (the attachment sites). NILVs are able to stably express transgenes from episomal DNA in non-dividing cells or transiently if the target cells divide. It has been shown that these vectors are able to transduce multiple cell types and tissues. These characteristics make NILVs ideal vectors to use in vaccination and immunotherapies, among other applications. They also open future prospects for NILVs as tools for the delivery of CRISPR/Cas9 components, a recent revolutionary technology now widely used for gene editing and repair.
Highlights
Lentiviral vectors have been developed and used in multiple gene and cell therapy applications
This review described the development of non-integrating lentiviral vectors (NILVs), achieved by mutating the viral integrase or the att sites in the viral DNA where this enzyme binds, and summarised the current and potential applications for these vectors
NILVs were developed to circumvent the potential insertional mutagenesis hazard posed by their integrating counterparts
Summary
Lentiviral vectors have been derived from human immunodeficiency virus-1 (HIV-1) and developed by segregating the necessary genetic information to form an infectious particle in different plasmids, while removing the capability for replication [1]. The transfer vector is the viral particle genome coding for the transgene of interest It is the only RNA in the cell that contains the HIV-1 packaging signal, enabling the specific packaging of this RNA into forming particles. The packaging plasmid codes for structural and enzymatic proteins necessary for particle formation and further viral life steps until the transfer vector is integrated into the target cell genome. CGD is characterised by a defect in the oxidative antimicrobial activity of phagocytes, resulting from mutations in the gp91(phox) gene It was observed in this gene therapy clinical trial that the insertional activation of MDS1-EVI1, PRDM16 and SETBP1 increased the expansion of the gamma-retroviral vector-corrected cells in the treated individuals, potentiating the clinical benefit to patients [17].
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