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0:00
Hello.
My name is Axel Schambach,
and I'm the acting director
of the Institute of
Experimental Hematology
at Hannover Medical School.
Within the next 40
to 45 minutes or so,
I would like to give
you a broad overview
on gammaretroviral vectors,
their biology, their design,
and their applications
in clinical trials.
0:23
I will structure my
presentation as follows.
I will start with an introduction
into the biology of retroviruses,
including their genome
and particle organization
and the retroviral life cycle.
From there I will give some insights
how retroviruses have developed
as evolutionary adapted vehicles
to deliver genetic information.
As a next step, we will
convert a retrovirus
into the retroviral
vector gene delivery tool
and mention how this vector
system has been efficiently used
in the clinical gene therapy arena.
We will also touch the
occurred adverse events
and how these would
potentially be prevented
in future gene therapy trials.
And mention the
development of SIN vectors
and how to create the
right therapeutic window
for gene therapy.
Apart from the integrating
retroviral vectors,
we will also mention
retroviral intermediates
as delivery tools for
genetic information.
And also in the end take you
a little bit on a time journey
into the field of retroviral gene
therapy and how it has developed.
Finally, I will conclude with a
summary and a take-home message.
1:30
So let's go into the details.
So what's so special about
retroviruses that makes them
attractive tools for gene transfer?
So first of all, retroviruses
are evolutionary optimized gene
carriers that have naturally
adapted to their host to efficiently
deliver genetic information
into target cells.
And as a hallmark and
common to all retroviruses,
they have the stage of
reverse transcription
of their single-stranded RNA
genome into double-stranded DNA.
And this double-stranded
DNA is then stably
integrated into the
host cell genome.
Looking back, they are highly
evolved parasites which exploit
the host cell machinery
for their own replication.
And it's maybe a
little bit surprising
to know that retroviruses are
already more than 8 million years
old and have been found already
back then in the mammalian genome.
The first approaches have been put
forward using retrovirus-based gene
transfer approximately 30 years ago.
Back then it has been shown that
it's much more efficient than DNA
transfection in primary cells
and that their use in murine bone
marrow transplantation
was quite successful
and paved the way for gene therapy
of the hematopoietic system.
