0:00
I want to welcome you
to this presentation.
My name is Nicola Brunetti-Pierri.
And I work as an
Associate Investigator
at the Telethon Institute
of Genetics and Medicine.
I'm also affiliated with the
Department of Translational
Medicine of Federico II
University in Naples, Italy.
In this talk, I would like
to bring your attention
to helper-dependent adenoviral
vectors and their applications
for gene therapy.
0:28
Adenoviruses are among
the most commonly
used vectors in human
clinical trials.
By 2012, over 420 clinical
trials were initiated
using adenoviral vectors
with the majority being
for cancer gene therapy.
0:46
Several vectors have been
investigated for gene therapy.
And so far, no single vector
system has yet emerged as clearly
superior to the others
for all applications.
This slide shows an overview
of the strengths and weaknesses
of adenoviral vectors compared to
the most commonly used vectors,
including retroviral
and lentiviral vectors,
AAV vectors and naked plasmid DNA.
1:12
Retroviral vectors can only
transduce dividing cells, requiring
a natural breakdown of the
nuclear membrane that occurs
during cell division,
to enter the nucleus.
Therefore, actively dividing
cells, such as hematopoietic stem
cells are excellent targets for
retroviral vector mediated gene
therapy, while tissues such as the
brain, eye, lung and adult liver
are not amenable for
in vivo gene delivery.
Following the infection
of target cells,
retroviral genome integrates
into the hostage genome,
particularly in sites closer to
transcriptionally active genes,
including proto-oncogenes.
Although integration provides the
potential for long term transgene
expression, because the
integrated genome is maintained
in the progenial
transduced cells, it also
increases the risks
of cancer formation
through insertional mutagenesis
or insertional activation
of proximal genes as it was observed
in the clinical gene therapy trial
for X-linked severe
combined immunodeficiency.
