Integrase deficient lentiviral vector: prospects for safe clinical applications

Abstract

HIV-1 derived lentiviral vector is an efficient transporter for delivering desired genetic materials into the targeted cells among many viral vectors. Genetic material transduced by lentiviral vector is integrated into the cell genome to introduce new functions, repair defective cell metabolism, and stimulate certain cell functions. Various measures have been administered in different generations of lentiviral vector systems to reduce the vector’s replicating capabilities. Despite numerous demonstrations of an excellent safety profile of integrative lentiviral vectors, the precautionary approach has prompted the development of integrase-deficient versions of these vectors. The generation of integrase-deficient lentiviral vectors by abrogating integrase activity in lentiviral vector systems reduces the rate of transgenes integration into host genomes. With this feature, the integrase-deficient lentiviral vector is advantageous for therapeutic implementation and widens its clinical applications. This short review delineates the biology of HIV-1-erived lentiviral vector, generation of integrase-deficient lentiviral vector, recent studies involving integrase-deficient lentiviral vectors, limitations, and prospects for neoteric clinical use.

Overexpression of salusin‑α upregulates AdipoR2 and activates the PPARα/ApoA5/SREBP‑1c pathway to inhibit lipid synthesis in HepG2 cells

“…First, the overexpression and interference salusin-α recombinant plasmids were constructed, after which they were packaged into 293T cells with the creation of overexpression and interference salusin-α lentiviruses for the infection of target cells, with the aim of directly upregulating or inhibiting the expression of salusin-α in cells at the genetic level. In addition, the target gene introduced by lentiviral construction cοuld be stably expressed in cells without disappearing as a consequence of cell division ( 26 , 27 ). Another advantage was that this system also eliminated experimental interference caused by other human factors, rendering it more a more accurate and convenient method for detecting subsequent signal pathway molecules.…”

Gene regulation in inborn errors of immunity: Implications for gene therapy design and efficacy

“…However, their ability to transduce cells tends to be lower than AAVs or other LVs, and their safety profile is not as well characterized. 23,49 And similar to AAV, IDLV's will not sustain durable expression in cells and tissues with high proliferative capacity.…”

“…Like AAVs, IDLVs can be designed with homology arms, combining the benefits of targeted gene therapy with lentiviral cargo capacity. However, their ability to transduce cells tends to be lower than AAVs or other LVs, and their safety profile is not as well characterized 23,49 . And similar to AAV, IDLV's will not sustain durable expression in cells and tissues with high proliferative capacity.…”

The Use of Natural Methods to Control Foodborne Biofilms

“…With more and more antibiotic-resistant bacterial strains emerging in biofilms, bacteriophages could be a powerful means to target the more persistent species while appearing to be safe themselves [ 22 ]. Genomic analyses demonstrated that STP55 has a short latent period and large burst size for hearty antimicrobial activity but lacks any antibiotic-resistance genes, virulence factor genes, or integrases that would permit a phage to integrate or harm the host genome [ 22 , 23 ]. Furthermore, phages are considered to be very consumer-friendly as they meet the qualifications to be labeled organic, kosher, or halal, thus expanding their versatility or reach in the food market [ 24 ].…”