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- 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
- Properties of retroviral vectors: I
- Properties of retroviral vectors: II
- Properties of retroviral vectors: III
- Properties of retroviral vectors: IV
- Innate immune recognition of retroviral vectors
- Lentiviral vectors - overview
- Lentiviral vectors - scientific rationale
- Nuclear import of viral genome
- Challenges of developing lentiviral vectors
- Lentiviral vectors - design
- Viral vector design
- Design of HIV-based vectors
- Third generation lentiviral vectors
- Lentiviral vector composition
- LV gene transfer
- Reducing HIV content of packaging system
- Self-inactivating transfer vectors
- HIV vector transcription in HIV-1 infected cells
- Lentiviral vector biosafety
- LV gene transfer - biosafety
- Lentiviral vectors: risk of insertional mutagenesis
Topics Covered
- Properties of retroviral vectors: Genetic stability in target cells, Transgene expression, Fidelity of replication, Target cell spectrum, Transdution efficiency, Toxicity, RCR or WT virus contamination, Integration, Immunogenicity
- Innate immune recognition of retroviral vectors
- Lentiviral vectors
- Nuclear import of viral genome
- Challenges of developing lentiviral vectors
- Viral vector design
- Design of HIV-based vectors
- Third generation lentiviral vectors
- Lentiviral vector composition
- Lentiviral gene transfer
- Reducing HIV content of packaging system
- Self-inactivating transfer vectors
- HIV vector transcription in HIV-1 infected cells
- Lentiviral vector biosafety
- Lentiviral vectors: risk of insertional mutagenesis
Talk Citation
Naldini, L. (2014, September 3). Lentiviral vectors: design, biological properties, milestones and current major applications, hazards 1 [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 14, 2024, from https://doi.org/10.69645/LWKC8146.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Luigi Naldini has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Lentiviral vectors: design, biological properties, milestones and current major applications, hazards 1
Published on September 3, 2014
58 min
A selection of talks on Genetics & Epigenetics
Transcript
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0:00
So hello, everybody.
This is Luigi Naldini from
the San Raffaele-Telethon
Institute of Gene
Therapy in Milan, Italy.
Today we will be discussing
properties of retroviral vectors
and, in particular,
lentiviral vectors.
0:18
The first slide, I'm
listing key properties
of retroviral vectors in general.
First of all, these vectors
are capable of integrating
the transgene into the genome.
So they're very well
suitable for stable gene
transfer in target cell.
Transgene expression can
also be stable in long term,
but this is not
necessarily the case.
At least in some situation, you
may have the vector gene stable
inserted in a cell, but
lack of its expression.
There is a number or
reason why this may happen.
In some cases, most of the vector
may be silenced, because the cell
can recognize viral sequence, most
often in the viral long terminal
repeat-- so-called LTRs--
and specifically silence
that by epigenetic changes.
This usually occurs
in some cell type--
most often embryonic stem cell.
And this usually happens with the
gamma retroviral vector, which
contains long terminal repeat,
which carries sequence which are
recognized by this
surveillance system.
So if you are
transducing ES cell, you
may want to use a vector which is
devoided of those long terminal
repeat sequence targeted by
the surveillance mechanism.
You may use a lentiviral
vector, or a vector
which has a deletion of those LTR.
In other cases,
silencing may only affect
a fraction of the integration site.
This could be a small
subset, or a sizable subset.
And these are those integration
which randomly occur into chromatin
being condensed, and so not
permissive to transcription;
or chromatin, which
becomes condensed
after that initial transduction.
In this case it will be
extinction of the O expression.
But most of the insertion site
could still be open and expressed.
So this statement about
general stability of expression
remains true, although not
for every insertion site,
but for a majority of
them in most of the cases.
In term of fidelity of
replication retroviral vector
are dependent on
reverse transcription
for the transfer of the
genome to target cell.
Reverse transcription
is highly error-prone
so there will be a significant
rate of mutation-- up
to one in thousand basis
In the transduced cell.
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