Registration for a live webinar on 'Innovative Vaccines and Viral Pathogenesis: Insights from Recent Monkeypox Research' is now open.
See webinar detailsWe noted you are experiencing viewing problems
-
Check with your IT department that JWPlatform, JWPlayer and Amazon AWS & CloudFront are not being blocked by your network. The relevant domains are *.jwplatform.com, *.jwpsrv.com, *.jwpcdn.com, jwpltx.com, jwpsrv.a.ssl.fastly.net, *.amazonaws.com and *.cloudfront.net. The relevant ports are 80 and 443.
-
Check the following talk links to see which ones work correctly:
Auto Mode
HTTP Progressive Download Send us your results from the above test links at access@hstalks.com and we will contact you with further advice on troubleshooting your viewing problems. -
No luck yet? More tips for troubleshooting viewing issues
-
Contact HST Support access@hstalks.com
-
Please review our troubleshooting guide for tips and advice on resolving your viewing problems.
-
For additional help, please don't hesitate to contact HST support access@hstalks.com
We hope you have enjoyed this limited-length demo
This is a limited length demo talk; you may
login or
review methods of
obtaining more access.
- Principles and general themes
-
1. Oncolytic viruses: strategies, applications and challenges
- Dr. Stephen J. Russell
-
2. Directed evolution of AAV delivery systems for clinical gene therapy
- Prof. David Schaffer
-
6. The host response: adaptive immune response to viral vector delivery
- Prof. Roland W. Herzog
-
7. Gene therapy and virotherapy in the treatment of cancer
- Prof. Leonard Seymour
-
8. Gene therapy for the muscular dystrophies
- Prof. Jeff Chamberlain
- Major gene transfer platforms and gene therapy strategies
-
9. Gammaretroviral vectors: biology, design and applications
- Prof. Axel Schambach
-
13. Surface-mediated targeting of lentiviral vectors
- Prof. Dr. Christian Buchholz
-
14. Gene transfer and gene therapy
- Dr. David A. Williams
-
15. Tracking vector insertion sites to explore the biology of transduced cells in vivo
- Prof. Dr. Christof Von Kalle
-
16. Advances in gene therapy for respiratory diseases 1
- Prof. John F. Engelhardt
-
17. Advances in gene therapy for respiratory diseases 2
- Prof. John F. Engelhardt
-
20. Gene therapy for hemophilia
- Prof. Katherine High
- New technologies for sequence-specific editing of gene expression
-
21. Helper-dependent adenoviral vectors for gene therapy
- Prof. Nicola Brunetti-Pierri
-
22. HSV vectors: approaches to the treatment of chronic pain
- Prof. Joseph C. Glorioso
- Archived Lectures *These may not cover the latest advances in the field
-
23. RNAi for neurological diseases
- Prof. Beverly L. Davidson
-
24. Directed evolution of novel adeno-associated viral vectors for gene therapy
- Prof. David Schaffer
Printable Handouts
Navigable Slide Index
- Introduction
- Overview
- In vivo and ex vivo gene therapy
- Cell entry modes of retroviral vectors
- Molecular functions of viral envelope proteins
- Early targeting attempts failed or very inefficient
- The current entry targeting concept
- Sindbis virus envelope protein based targeting
- Binding sites on measles virus (MV) hemagglutinin
- Non-targeted and targeted lentiviral (LV) vectors
- Targeting domains and specificities
- High specificity of the targeting system
- Lymphocyte specific lentiviral vectors
- Transduction of lymphocytes by MV-LV vectors
- Generation of CD8-LV from hybridoma cell line
- T-cell receptor (TCR) gene transfer by CD8-LV
- TCR gene transfer by CD8-LV & tumor cell killing
- CD8-LV-transduced cells have higher CD8 levels
- Reasons for enhanced killing of tumor cells
- Haematopoietic stem cell targeting with CD133-LV
- CD133-LV has high target specificity at high dose
- Transduction of primary haematopoietic stem cells
- Transduction of stem cells in mixed cultures
- In vivo targeting: local vs. systemic administration
- Targeting the murine glutamate receptor
- GluR-LV specifically targets neurons
- In vivo injection of GluR-LV vector particles
- Transduction of NeuN but not GFAP positive cells
- Injection into the hippocampus
- Targeted gene transfer to endothelial cells
- CD105-LV & specific endothelial cells (LSEC)
- Systemic application of mCD105-LV
- CD105-LV targets small capillaries made by LSEC
- mCD105-LV transduces LSEC, not Kupffer cells
- Intra-tumoral application targets tumor endothelium
- Efficient gene transfer into human LSEC
- In vivo transduction of transplanted human artery
- Conclusions
- Tumor targeting in adeno-associated virus (AAV)
- Acknowledgements
Topics Covered
- In vivo and ex vivo gene therapy
- Cell entry modes of retroviral vectors
- Molecular functions of viral envelope proteins
- Introduction to surface targeting
- Targeting subtypes of lymphocytes and hematopoietic stem cells (Ex vivo)
- In vivo targeting (local vs. systemic administration)
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Buchholz, C. (2014, August 5). Surface-mediated targeting of lentiviral vectors [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 7, 2024, from https://doi.org/10.69645/BLJX2976.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Dr. Christian Buchholz has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Biochemistry
Transcript
Please wait while the transcript is being prepared...
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.