0:00
My name is Frederic Bushman.
I'm a professor at the
University of Pennsylvania.
And the title of this lecture is
Vector Integration Preferences
and Integration Site Analysis.
0:12
This lecture will begin with an
introduction, just a little bit
about gene therapy and
vector integration.
Then methods for
monitoring gene transfer.
Then HIV integration targeting.
Then gammaretroviral integration
targeting, which differs.
And lastly, analysis of vector
integration in human gene therapy.
0:35
Next slide shows the general
idea of stem cell gene therapy
to treat an inherited disease.
So bone marrow cells are
removed from the patient,
and then gene-corrected
by transduction ex vivo
with retroviral vector that
encodes the corrective gene, shown
in the upper left.
So that installs the corrective
gene into bone marrow cells,
lower left, where each cell
now has the vector integrated
at a different location
in the human genome.
You can then re-infuse those
cells into the subject.
And bone marrow cells
produce daughter
cells, which circulate in the blood.
You can then sample
cells from blood years
later, shown on the
right, and sequence
integration site distributions.
And that can tell you things like
how many different kinds of cells;
how many different progenitor
cells or contributing cells
to the periphery; and whether
some cells are contributing more
than others; and in cases
of adverse events, leukemia,
you can tell where the
integration site was
and get some information
on the genes involved.
So stem cell gene therapy has been
used to treat many subjects now
with inherited immuno-deficiencies
and other conditions.
