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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.
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
And ex vivo activation
in prolonged culture
has been shown, especially when
using imperfect methodology
in experiment, to
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.