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Hello to all.
My name is Dr. Takis Athanasopoulos
from GlaxoSmithKline.
I'm the Acting Head
of Patient Operations
in Cell and Gene Therapy
at GSK in Stevenage, UK.
The focus of our talk
today will be on the
recent advances in
the development
of gene delivery technologies.
It is an important
goal in the research
of gene delivery systems to develop
clinically relevant vectors
that we can use to combat
a lot of diseases.
We have quite a few
HIV, AIDS, cancer, Alzheimer's
and monogenic diseases.
DNA or RNA-based viral
vector systems utilise
these viral or non-viral
vector technologies
to deliver genetic
materials to host cells.
It is an efficient way to
deliver the genetic material
and we will be capturing some of these
recent technologies as part of our talk.
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Depicted here are some of the
critical factors that are
required for a successful
cell and gene therapy.
In terms of delivery,
a viral or non-viral
vector has lots
of cell structures and defences
to beat during their uptake.
They have to utilise
their cellular receptors,
or co-receptors,
but in order to work, it's
trafficked towards the cell.
There it will interact
with multiple organelles,
depending on whether it
is a DNA or RNA vector.
The eukaryotes include
animals, plants and fungi,
and we have multiple organelles
with various functions.
For example,
the nucleolus that
makes the ribosomes,
the mitochondria which are the
energy producers of the cell,
the Golgi complex, an apparatus
that processes proteins and lipids
and are useful for the
secretion of the cell,
and microtubules that are for
structural movement and cell division.
The rough and the smooth endoplasmic
reticulum for lipid synthesis and metabolism,
and lysosomes and
various other vesicles.
Of importance to all these
critical structures,
and from a gene
transfer perspective,
is the uptake of the vector
by appropriate cells,
but also the subsequent
steps, i.e., the vector entry
into the nucleus if it is a DNA vector,
or the cytoplasm if it is an RNA vector.
Of paramount importance,
from a gene transfer
perspective,
is the evasion of
host immune defences.
One of the factors required for
successful cell and gene
therapy transgene delivery
is that the vector has to evade
the host immune defences.
These evasions are
of multiple natures.
It can be an innate
response with
subsequent release of
pro-inflammatory cytokines,
recruitment of
neutrophils, macrophages,
dendritic cells or
other leukocytes,
and activation and maturation
of antigen-presenting cells.
It can also involve adaptive priming
through dendritic cell activation
or adaptive responses.
All of these are very important.
From a cell and gene transfer
delivery perspective,
we want to abdicate or eliminate
any unwanted immune responses.
