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0:00
This is Christian Buchholz at the
Molecular Biotechnology and Gene
Therapy section at the Paul-Ehrlich
Institute in Langen, Germany.
I'm very pleased to
present the lecture
on surface-mediated targeting
of lentiviral vectors.
0:15
I have divided the lecture
into the topics listed here.
We'll start with an
introduction into surface
targeting of immuno viruses.
I will then show you a series of
examples covering a broad variety
of target subtypes, including
lymphocytes, hematopoietic stem
cells, neurons, and
endothelial cells.
We will first focus on
ex vivo applications
and then go through
some examples of in vivo
administrations of
the targeted vectors.
0:42
In gene therapy, we do basically
distinguish between in vivo
and ex vivo modification
of target cells.
By in vivo, we mean that vectors are
directly injected into the patient,
which can be locally, such as
intracerebrally, or systemically.
Ex vivo means that target cells
are removed from the patient then
transduced ex vivo
in culture vessels
before they will be
re-implanted into the patient.
It is obvious that upon
in vivo applications,
vectors will encounter a
large variety of cell types
besides the actual target
cells relevant for therapy.
However, also ex vivo, primary cells
are not homogeneous and may well
differ, for example, in
the differentiation state.
Targeting vector particles
to the relevant cell type
without losing particles
to non-relevant cells
is therefore an important
goal in vector engineering.
Only surface targeting of vector
particles may make this possible.
1:38
To understand the strategies
to achieve surface targeting,
we first have to look at the entry
routes of retroviral vectors.
Retroviral vectors
are envelope particles
that bind with their surface
receptor for cell entry.
Both entry modes, pH-independent
on the left, and pH-dependent
on the right, the barrier of
particle actin has to be passed.
We will actually come back to
this later in this lecture.
Moreover, in each entry mode,
fusion of the viral and the cellular
membranes, which is the
plasma membrane in A
and the endosomal
membrane in B, is required
to release the genetic
information into the cell.
This is a tightly regulated process
which can be induced by low pH
or, as in the case of anti-viruses
and also measles virus,
by receptor contact.
The molecular basis behind this
is illustrated on the next slide.
