A Sight for Sore Eyes: Using Gene Therapy and Gene Editing to Treat Blindness

April 21st, 2016 by FFB Canada

Story guest authored by Erik Fraunberger, a neuroscience graduate student at the Alberta Children’s Health Research Institute in Calgary, Alberta.

We live in exciting times! With each passing day, we get one step closer to safely and effectively treating the vision diseases that affect more than a million Canadians. In recent years, scientists and clinicians have been collaborating to develop treatments that repair or replace malfunctioning, disease-causing genes. This story unpacks the complex science of genetics to answer the question: What is the difference between gene therapy and gene editing, and what does it mean for me?

You may have heard the terms “gene therapy” and “CRISPR” being tossed around in the media next to “revolutionary.” Calling something revolutionary is certainly bold, but in the case of CRISPR, most agree that this label is well justified. Why? What is so revolutionary about CRISPR? To answer this question, we first need to take a step back and examine traditional gene therapy, which, at its core, uses genetics to treat illness. On the surface, taking a genetic approach to treating disease is challenging because for a long time, we assumed that you could not change your genetic makeup. In other words, your genes are the cards you are dealt and you don’t get a chance to shuffle them around. While this is generally true, researchers have been able to take advantage of our knowledge of the structure of DNA to bend the rules.

Since our genetic code prefers to store information in combinations of three, think of a genetic mutation as the odd card out in what would otherwise be a sort of three-of-a-kind. Isn’t it frustrating when you are one card away from that three-of-a-kind? Your cells think so too! Fortunately, this is where gene therapy comes in to give you that winning hand, or biologically speaking, functional genes and healthy cells. There are two common ways in which scientists accomplish this: conventional gene therapy and CRISPR. While both techniques modify our genes, they both do so in different ways.

Conventional Gene Therapy

Whenever you read the term “gene therapy”, it is usually referring to the use of viruses (or tiny synthetic containers) to deliver a whole, replacement gene to a person’s cells. This way, even though the malfunctioning gene is still present, the new and healthy copy of the gene is inserted to fix the problem.  This is very similar to taking a medication in that a regular dose is required to maintain the effect. However, just like any medication, there are downsides. For example, the virus that is used to deliver the gene may cause an immune response. In addition, viruses are not able to deliver very large genes. Therefore, this approach only works for smaller genes.

What about CRISPR?

A more recent gene therapy technology that you may have encountered is the CRISPR/Cas9 system. This excellent example of biological engineering was originally discovered in bacteria, where it functions as a sort of immune system, which protects bacteria from viruses. Basically, bacteria use the CRISPR/Cas9 system to identify and get rid of viral DNA. How does it work? The CRISPR/Cas9 system has two key components: 1) a set of genetic scissors that is able to cut DNA and, 2) guides that show these scissors where to cut. By putting these two components to work, bacteria use the CRISPR/Cas9 system to cut up viral DNA as it enters the cell. As a therapeutic tool to treat eye disease, scientists have been able to modify CRISPR to cut out a mutated gene. They are also able to use CRISPR/Cas9 to paste in a non-mutated copy of the same gene. However, this is easier said than done. Before this can be tested in humans, scientists need to make sure that there are no “off-target effects.” This is because there is a possibility of accidentally cutting out the wrong segment of DNA! If this happened, the end result might be a new disease-causing mutation. This is why scientists and clinicians are proceeding with caution.

Putting it all Together

Despite these limitations, the incredible pace of clinical and preclinical advancements shows no sign of slowing down! In fact, several clinical trials are currently in progress around the world, including within Canada, to show that it is possible to safely and effectively deliver genes into the eye to treat diseases such as choroideremia and retinitis pigmentosa (RP). Even the biotechnology industry is seeing the potential in gene therapy as RetroSense Therapeutics is testing its new gene therapy for RP in a phase I/II clinical trial. In the lab, thanks in part to the funding provided by the FFB, Dr. Andras Nagy has creatively combined gene editing techniques with stem cell based therapy to develop a novel treatment for wet age related macular degeneration. We can expect to see many more applications of gene therapy and gene editing to treat vision diseases in the coming years.


Conventional’ Gene Therapy
1. Well researched in animal models
2. Wide variety of administration methods available
3. Clinical trials are underway
1. Very precise editing of genes
2. Can edit genes of varying size
3. Modified in the lab to increase efficiency


Conventional’ Gene Therapy
1. Requires constant dosing over the lifetime
2. Difficult to have incorporation into all affected cells
1. Off-target errors can cause harm
2. More pre-clinical trials needed to adequately assess safety

MacLaren RE, Groppe M, Barnard AR, et al. Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. Lancet. 2014;383(9923):1129-1137.

Bassuk AG, Zheng A, Li Y, Tsang SH, Mahajan VB. Precision Medicine: Genetic Repair of Retinitis Pigmentosa in Patient-Derived Stem Cells. Sci Rep. 2016;6:19969.
Therapeutics R. RST-001 Phase I/II Trial for Retinitis Pigmentosa. 2016.
Michael IP, Westenskow PD, Hacibekiroglu S, et al. Local acting Sticky-trap inhibits vascular endothelial growth factor dependent pathological angiogenesis in the eye. EMBO Mol Med. 2014;6(5):604-623.
Hung S, Chrysostomou V, Fan-Li A, et al. CRISPR/Cas-mediated gene editing of retinal cells in vivo. Bio Rxiv. 2016.