UCL Institute of Ophthalmology Department of Genetics
Gene therapy for eye disease
• An experimental technique that uses the
delivery of genetic material to treat or
prevent disease by:
• Delivering a working copy of a
damaged gene that causes disease –
gene supplementation therapy
• Inactivating, or “knocking out,” a
mutated gene that is functioning
improperly – gene silencing
• Introducing a new gene into the body
to help fight a disease –
neuroprotection or angiostatic
therapy
What is gene therapy?
• A carrier called a vector delivers the
therapeutic gene to the patient's target cells –
the most common vector is a virus that has
been genetically altered to carry the
therapeutic gene.
• Which vector we choose to use depends on the
cells we want to target and the size of the gene
we wish to deliver to these cells.
• The three types of virus usually used to study
gene therapy in the eye are lentivirus (such as
HIV), adenovirus and adeno-associated virus
(AAV).
Adeno-associated virus (AAV)
• AAV is the most commonly-used vector, as it is not harmful
even in its "wild" form.
• AAV efficiently delivers genes to light-sensitive photoreceptor
cells and the underlying retinal pigment epithelium (RPE),
making it an ideal gene therapy vector for inherited retinal
disorders
When injected under the retina, AAV
efficiently delivers a reporter gene,
encoding Green Fluorescent Protein,
to photoreceptor and RPE cells
Direct injection of viral vectors into the eye.
• For our gene therapy clinical trials, the surgical procedure
involves injecting the virus under the retina, producing a
temporary retinal detachment
• Recovery time is usually rapid and it is often possible to go
home the same day
• Quality of sight is reduced temporarily until recovery is
complete, which is usually expected to take a few weeks.
Targeting different cells in the eye
• Ideally, the therapeutic gene should only be delivered to the
cells that would naturally produce this protein
• The vector may infect many cell types when it is injected, so by
using a cell-specific promoter, we can restrict gene expression
to certain cell types within a tissue:
(a) photoreceptor cells and
RPE; (b) RPE only, (c) cone
photoreceptor cells only; (d),
(e) corneal cells and (f)
Muller cells in the inner
retina