Lentiviral vectors: design, biological properties, milestones and current major applications, hazards 2

Published on September 3, 2014   38 min

Other Talks in the Category: Diseases, Disorders & Treatments

0:04
The next slide, we are now shifting gears and describing what are the most commonly seen applications today in the lentiviral vector in clinical testing. And now we start from discussing ex vivo application into hematopoietic cell gene therapy in particular hematopoietic stem cell gene therapy.
0:27
The next slide shows and summarizes the fact that several work from the early days after the developmental of the lenvitiral vectors show that, indeed, this vector had a benefit of improved gene transfer into hematopoietic stem cell. And this is mostly due to the fact that because, as mentioned several times, lentiviral vectors do not rely on active proliferation of the site at the time of infection, they don't require as much culture ex vivo and as much proliferation of the cell that they infect as the gamma lentiviral vector do. This is particularly relevant when handling hematopoietic stem cell because these cells are, first of all, primarily quite reticent when they are in the bone marrow of a host. Upon harvesting an ex vivo transduction, they may need to be activated. However, when using the lentiviral vector, there is not a strict need for this cell to enter proliferation nor to be maintained in culture for several days to achieve efficient infection like it had to be done with the gamma lentiviral effect. And ex vivo activation in prolonged culture has been shown, especially when using imperfect methodology in experiment, to induce differentiation or even it extinguishes the stem cell properties. And so lentiviral vector allows a much more efficient infection, which translate into shorter ex vivo culture, which means when these transducers are transplanted into recipients into a polyclonal, a more efficient repopulation of the host by gene-corrected cell. This has been shown both in mice transplanted with mouse cells, as well as in mice transplanted with human cells in an American experiment, and very recently in humans transplanted with human cells in clinical trials. And you see the main early work in the reference listed below. Similarly because the lentiviral vector efficiently transduced non-dividing cells, it has also been shown to be good at transducing tissue in vivo, including the central nervous system right in the liver. We will discuss this later on.
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Lentiviral vectors: design, biological properties, milestones and current major applications, hazards 2

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