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Printable Handouts
Navigable Slide Index
- Introduction
- Using viral vectors for gene therapy
- Immune system vs. gene therapy
- Neutralizing antibody against viral vectors
- Activation signals for the immune system
- Immune privilege in the eye
- B and T cell responses in viral gene transfer
- Factors that increase immune responses
- Lentiviral vectors
- Transduction of APCs by lentiviral vector
- De-targeting of transgene expression from APCs
- Adeno-associated virus (AAV) vectors
- T cell response to ovalbumin after gene transfer
- Impact of the underlying mutation
- Immune suppressive drugs
- Transient immune suppression - implication
- Immune tolerance induction by AAV gene transfer
- Hepatic AAV gene transfer induces tolerance
- Hepatic F.IX gene transfer trial result
- CTL responses to AAV capsid in humans
- Sensing and processing of AAV vector particles
- CTL responses to AAV gene transfer
- Immune suppression controls anti-capsid T cells
- AAV gene transfer avoids immune responses (1)
- AAV gene transfer avoids immune responses (2)
- Decoy capsids for gene transfer with NAbs
- Ways to avoid rejection by the immune system
- Acknowledgements
Topics Covered
- Gene therapy using viral vector
- Risk of immune responses specific to vector or transgene product
- Pre-existing immunity to viral vectors due to natural infection
- Design of vectors to minimize or entirely avoid B and T cell responses
- Modification of gene transfer protocols to minimize/avoid/circumvent B and T cell responses
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Herzog, R.W. (2014, August 5). The host response: adaptive immune response to viral vector delivery [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 21, 2024, from https://doi.org/10.69645/URGO8255.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Herzog serves on the scientific advisory board of Ally Therapeutics. He has received royalties from Takeda Pharmaceuticals for oral tolerance technologies and grant funding from Luye R&D for gene therapy research.
A selection of talks on Genetics & Epigenetics
Transcript
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0:00
My name is Roland Herzog.
I'm a professor at the University
of Florida Department of Pediatrics
at the Powell Gene Therapy Center
where we are developing gene
therapies for genetic
disease using viral vectors
to transfer our therapeutic genes.
One of the key questions that
we're addressing in my laboratory
is what do we have to do to
avoid rejection of our therapy
by the immune system?
So understanding the adaptive immune
response to viral gene transfer
is key for sustained therapy and
successful delivery of our genes.
0:42
The concept of viral gene
transfer is quite simple.
We use recombinant viruses
which we engineered to contain
a therapeutic gene that could
correct a genetic defect.
Viruses have evolved to effectively
infect a variety of cell types.
So we can choose and
design these viral vectors
to infect a certain type
of cells and express
our therapeutic gene in those cells.
1:12
However, a potential
complication of this approach
is that the immune system has
evolved to fend off versus
and to recognize viruses
as invading pathogens.
Shown here is an example of
a muscle fiber, shown in red,
which expresses a gene
that we transferred
in using a viral vector.
And this cell is being surrounded
by these green cells, which
are cytotoxic T lymphocytes--
CD8 positive T cells that
attack and destroy
this muscle fiber.
So in this case, the immune
system has rejected our therapy.