1. Gene therapies: a short
introduction to the
underlying science for
REC members
Gene therapies: techniques that
modify our genes / genetic code
to treat disease.
Some examples
and to end, some comments on the consequences for ethical review
2. Amino acid – the building block for our
proteins
DNA – deoxyribonucleic acid, our basic
genetic code in the nuclei of our cells
Gene - sequences of DNA that code for a
protein
Gene editing – changing our DNA using
specific tools
Integrating - a gene therapy that is inserted
INTO our DNA (cf NON-Integrating)
Liposome - a sac of fatty molecules designed
to carry genetic material into our cells
Plasmid - a small circular DNA strand in a
bacterium.
Peptides – short sequences of amino acids
Polymer - substance built up mainly of similar
units bonded together,
RNA – ribonucleic acid – the messenger that
takes the DNA code to other parts of the cell so
we can make proteins
Virus – natural infectious particles that can get
into our cells
Key words we use
3. What do gene therapies do?
• Replace / modify a
diseased gene with a
healthy copy.
• Inactivate a disease-
causing gene
• Stimulate immunity to
infections (vaccination) or
cancers (immuno-
oncotherapy).
• Programme (harmful) cells
to die.
4. Sounds very complicated!
But RECs don’t need a deep
understanding. This can be
provided by experts within and
outside the committee.
However, a basic grasp of the
subject makes review easie,
more fun and more rewarding.
5. Some biology
RNA – the
messenger that
takes the code to
the protein factory
(ribosomes)
DNA – our genetic
code from our
parents
Proteins – the
body’s building
blocks that “make
us us”
6. How they do it 1
Correcting errors in the code
by
“mending”
the DNA
inserting new
DNA*
inserting new
RNA
*Integrating
OR non-
integrating
7. How they do it 2
IN-vivo: using
a “vector”, to
put genetic
material into
our cells.
EX-vivo: taking
cells out of our
body then
manipulating
their genetic
makeup.
Then putting them back!
8. How they do it 3
Gene editing: repairing the
genetic material using cutting
and repairing tools (enzymes)
10. Vectors
Getting genetic material into
our cells isn’t simple.
We need transport
mechanisms – “vectors”
We can roughly classify them
into two types
• Viral
• Non viral
11. Viral Vectors 1
The virus capsule
The virus’ genetic material
altered to carry the genes
we want to put into the cell
13. Non-viral Vectors
• Naked DNA
• DNA wrapped up to make a
particle that will be taken up
by cells
• Liposomes
• Self assembling polymers
• Self assembling peptides
• Combinations of the above
These (viral and
non viral) have their
own advantages
and disadvantages.
14. Host DNA with mutation
Changing the genetic
material 1
No or Non-functioning
protein – the illness
The problem
15. Wild-type DNA
Host DNA with mutation
Changing the genetic
material 2
Adding a correct
DNA sequence
(non-integrating)
No or Non-functioning
protein – the illness
The solution
Functioning
protein
16. Wild-type DNA
Host DNA with mutation
Adding a correct
DNA sequence
(integrating)
The solution
Functioning
protein
Changing the genetic
material 3
No or Non-functioning
protein
17. Host DNA with mutation
Preventing
expression of a
harmful protein
The solution
Changing the genetic
material 4
RNA inhibitors
19. mRNA coding for part of a virus
Host cell
Vaccine
development:
an area in which
gene therapy is
playing a part.
Changing the genetic
material 6
mRNA
“Viral pieces” which the
bodies immune system
makes antibodies to
20. Gene editing;
inserting enzymes
(eg CRISPR) to
mend the DNA
The problem
Editing the genetic
material 1
Host DNA with mutation
Non-functioning
protein
21. Gene editing;
inserting enzymes
(eg CRISPR) to
mend the DNA
The solution
Editing the genetic
material 2
Host DNA with mutation corrected!
Gene editing tool eg CRISP
Functioning
protein
22. Consequences for ethical review
SOMEONE CALLED A
BIOETHICIST IS HERE TO SEE
YOU!
Most research harm is
a result of scientific
rather than “ethical”
failure.
23. Gene therapy, science and
the ethical consequences
• Benefits and harms rest on the
choice of vector and the gene
therapy.
• Consent processes must
accommodate novelty,
uncertainty, possible
complexity and the patients’
predicament (therapeutic
desperation).
Consequences for ethical review
25. back to the beginning
You’ll find further references at the bottom of the webpage.
Particular thanks to Rosie Munday, Andrew George, Joost van
Haasteren, Tiong Tan and all on Oxford A NHS REC
The end (of this
introduction)
Editor's Notes
Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use 1.
These are techniques that modify a person’s genes to treat or cure disease. They can work by several mechanisms:
Replacing a disease-causing gene with a healthy copy of the gene
Inactivating a disease-causing gene that is not functioning properly
Introducing a new or modified gene into the body to help treat a disease
Gene therapy products are being studied to treat diseases including cancer, genetic diseases, and infectious diseases.
There are a variety of types of gene therapy products, including:
Plasmid DNA: Circular DNA molecules can be genetically engineered to carry therapeutic genes into human cells.
Viral vectors: Viruses have a natural ability to deliver genetic material into cells, and therefore some gene therapy products are derived from viruses. Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors (vehicles) to carry therapeutic genes into human cells.
Bacterial vectors: Bacteria can be modified to prevent them from causing infectious disease and then used as vectors (vehicles) to carry therapeutic genes into human tissues.
Human gene editing technology: The goals of gene editing are to disrupt harmful genes or to repair mutated genes.
Patient-derived cellular gene therapy products: Cells are removed from the patient, genetically modified (often using a viral vector) and then returned to the patient.
Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use 1.
These are techniques that modify a person’s genes to treat or cure disease. They can work by several mechanisms:
Replacing a disease-causing gene with a healthy copy of the gene
Inactivating a disease-causing gene that is not functioning properly
Introducing a new or modified gene into the body to help treat a disease
Gene therapy products are being studied to treat diseases including cancer, genetic diseases, and infectious diseases.
There are a variety of types of gene therapy products, including:
Plasmid DNA: Circular DNA molecules can be genetically engineered to carry therapeutic genes into human cells.
Viral vectors: Viruses have a natural ability to deliver genetic material into cells, and therefore some gene therapy products are derived from viruses. Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors (vehicles) to carry therapeutic genes into human cells.
Bacterial vectors: Bacteria can be modified to prevent them from causing infectious disease and then used as vectors (vehicles) to carry therapeutic genes into human tissues.
Human gene editing technology: The goals of gene editing are to disrupt harmful genes or to repair mutated genes.
Patient-derived cellular gene therapy products: Cells are removed from the patient, genetically modified (often using a viral vector) and then returned to the patient.
Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use 1.
These are techniques that modify a person’s genes to treat or cure disease. They can work by several mechanisms:
Replacing a disease-causing gene with a healthy copy of the gene
Inactivating a disease-causing gene that is not functioning properly
Introducing a new or modified gene into the body to help treat a disease
Gene therapy products are being studied to treat diseases including cancer, genetic diseases, and infectious diseases.
There are a variety of types of gene therapy products, including:
Plasmid DNA: Circular DNA molecules can be genetically engineered to carry therapeutic genes into human cells.
Viral vectors: Viruses have a natural ability to deliver genetic material into cells, and therefore some gene therapy products are derived from viruses. Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors (vehicles) to carry therapeutic genes into human cells.
Bacterial vectors: Bacteria can be modified to prevent them from causing infectious disease and then used as vectors (vehicles) to carry therapeutic genes into human tissues.
Human gene editing technology: The goals of gene editing are to disrupt harmful genes or to repair mutated genes.
Patient-derived cellular gene therapy products: Cells are removed from the patient, genetically modified (often using a viral vector) and then returned to the patient.
Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use 1.
These are techniques that modify a person’s genes to treat or cure disease. They can work by several mechanisms:
Replacing a disease-causing gene with a healthy copy of the gene
Inactivating a disease-causing gene that is not functioning properly
Introducing a new or modified gene into the body to help treat a disease
Gene therapy products are being studied to treat diseases including cancer, genetic diseases, and infectious diseases.
There are a variety of types of gene therapy products, including:
Plasmid DNA: Circular DNA molecules can be genetically engineered to carry therapeutic genes into human cells.
Viral vectors: Viruses have a natural ability to deliver genetic material into cells, and therefore some gene therapy products are derived from viruses. Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors (vehicles) to carry therapeutic genes into human cells.
Bacterial vectors: Bacteria can be modified to prevent them from causing infectious disease and then used as vectors (vehicles) to carry therapeutic genes into human tissues.
Human gene editing technology: The goals of gene editing are to disrupt harmful genes or to repair mutated genes.
Patient-derived cellular gene therapy products: Cells are removed from the patient, genetically modified (often using a viral vector) and then returned to the patient.
Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use 1.
These are techniques that modify a person’s genes to treat or cure disease. They can work by several mechanisms:
Replacing a disease-causing gene with a healthy copy of the gene
Inactivating a disease-causing gene that is not functioning properly
Introducing a new or modified gene into the body to help treat a disease
Gene therapy products are being studied to treat diseases including cancer, genetic diseases, and infectious diseases.
There are a variety of types of gene therapy products, including:
Plasmid DNA: Circular DNA molecules can be genetically engineered to carry therapeutic genes into human cells.
Viral vectors: Viruses have a natural ability to deliver genetic material into cells, and therefore some gene therapy products are derived from viruses. Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors (vehicles) to carry therapeutic genes into human cells.
Bacterial vectors: Bacteria can be modified to prevent them from causing infectious disease and then used as vectors (vehicles) to carry therapeutic genes into human tissues.
Human gene editing technology: The goals of gene editing are to disrupt harmful genes or to repair mutated genes.
Patient-derived cellular gene therapy products: Cells are removed from the patient, genetically modified (often using a viral vector) and then returned to the patient.
Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use 1.
These are techniques that modify a person’s genes to treat or cure disease. They can work by several mechanisms:
Replacing a disease-causing gene with a healthy copy of the gene
Inactivating a disease-causing gene that is not functioning properly
Introducing a new or modified gene into the body to help treat a disease
Gene therapy products are being studied to treat diseases including cancer, genetic diseases, and infectious diseases.
There are a variety of types of gene therapy products, including:
Plasmid DNA: Circular DNA molecules can be genetically engineered to carry therapeutic genes into human cells.
Viral vectors: Viruses have a natural ability to deliver genetic material into cells, and therefore some gene therapy products are derived from viruses. Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors (vehicles) to carry therapeutic genes into human cells.
Bacterial vectors: Bacteria can be modified to prevent them from causing infectious disease and then used as vectors (vehicles) to carry therapeutic genes into human tissues.
Human gene editing technology: The goals of gene editing are to disrupt harmful genes or to repair mutated genes.
Patient-derived cellular gene therapy products: Cells are removed from the patient, genetically modified (often using a viral vector) and then returned to the patient.
Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use 1.
These are techniques that modify a person’s genes to treat or cure disease. They can work by several mechanisms:
Replacing a disease-causing gene with a healthy copy of the gene
Inactivating a disease-causing gene that is not functioning properly
Introducing a new or modified gene into the body to help treat a disease
Gene therapy products are being studied to treat diseases including cancer, genetic diseases, and infectious diseases.
There are a variety of types of gene therapy products, including:
Plasmid DNA: Circular DNA molecules can be genetically engineered to carry therapeutic genes into human cells.
Viral vectors: Viruses have a natural ability to deliver genetic material into cells, and therefore some gene therapy products are derived from viruses. Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors (vehicles) to carry therapeutic genes into human cells.
Bacterial vectors: Bacteria can be modified to prevent them from causing infectious disease and then used as vectors (vehicles) to carry therapeutic genes into human tissues.
Human gene editing technology: The goals of gene editing are to disrupt harmful genes or to repair mutated genes.
Patient-derived cellular gene therapy products: Cells are removed from the patient, genetically modified (often using a viral vector) and then returned to the patient.
Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use 1.
These are techniques that modify a person’s genes to treat or cure disease. They can work by several mechanisms:
Replacing a disease-causing gene with a healthy copy of the gene
Inactivating a disease-causing gene that is not functioning properly
Introducing a new or modified gene into the body to help treat a disease
Gene therapy products are being studied to treat diseases including cancer, genetic diseases, and infectious diseases.
There are a variety of types of gene therapy products, including:
Plasmid DNA: Circular DNA molecules can be genetically engineered to carry therapeutic genes into human cells.
Viral vectors: Viruses have a natural ability to deliver genetic material into cells, and therefore some gene therapy products are derived from viruses. Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors (vehicles) to carry therapeutic genes into human cells.
Bacterial vectors: Bacteria can be modified to prevent them from causing infectious disease and then used as vectors (vehicles) to carry therapeutic genes into human tissues.
Human gene editing technology: The goals of gene editing are to disrupt harmful genes or to repair mutated genes.
Patient-derived cellular gene therapy products: Cells are removed from the patient, genetically modified (often using a viral vector) and then returned to the patient.
