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According to a study, nanotechnology, already used in RNA-based vaccines, could lead to a new approach to gene therapy and ultimately improve the treatment of hereditary forms of blindness.
Improving gene therapy based on adenoviruses
Treatment for hereditary blindness may well take a big leap soon. In 2017, a first gene therapy to treat a hereditary form of blindness was approved by the Food and Drug Administration (FDA) in the United States. The idea was to use a modified version of an adenovirus or AAV, to deliver DNA strands correcting the defective genes and thus stopping this hereditary blindness. Many patients have benefited from an improvement in their vision.
But these gene therapies have certain limitations: the AAV virus is relatively small and cannot physically contain certain complex mutations. To circumvent this limitation, a collaborative team of researchers from Oregon Health & Science University developed a new approach, based on research done on mRNA vaccines against COVID-19.
Lipid nanoparticles, a tool to better target the photosensitive cells of the eye
So the team set out to use lipid nanoparticles, tiny balls of fat made in the lab, to deliver strands of messenger ribonucleic acid, or mRNA, directly into the eye. These lipid nanoparticles do not have the same size constraints as adenoviruses. In addition, the delivery of mRNA (and no longer DNA) reduces the risks of off-target protein production, due to its limited lifespan.
There still remained the challenge of successfully delivering these nanoparticles to the retina. For this, the researchers surrounded their nanoparticles with an envelope of specific pepties which allows them to be “directed” towards the photoreceptor cells of the retina, a tissue located at the back of the eye which allows vision.
After injecting their masterful cocktail into the eyes of animal models, the research team used various imaging techniques to examine the treated eyes. The first tests are conclusive and confirm that the mRNA has indeed reached its target. They are still working to better assess the amount of protein produced in the retina.
A promising alternative for various retinal diseases
Despite the very encouraging results of their first trials, the researchers foresee a long and exciting road ahead in research against hereditary blindness.
“Improved technologies used for gene therapy may provide more treatment options to prevent blindness. The results of our study show that lipid nanoparticles could help us do this.” they confirm.
To date, in fact, more than 250 genetic mutations have been linked to inherited retinal diseases, but only one has an approved gene therapy.
But a step forward that will still take a long time
For Professor Antoine Brezin, ophthalmologist and member of our Doctissimo expert committee, the study plays more on an announcement effect than on the probability of restoring sight to blind people… At least for the moment:
“This is ultra preliminary research. The problem of gene therapy is to manage to put in a cell either the mRNA or the protein, in any case what is needed so that the protein which does not work is finally delivered. What is approved in a single case and also does not work miracles are adenoviruses. Here, what the researchers tried to do was lipid nanoparticles which, in their animal model, enter neurosensory cells of the retina, without them really knowing which ones. From there, the number of extrapolations it would take to consider human benefits is very high!”
A precipitation that the professor criticizes a little for today’s science:
“We are used to it: these researchers and these technological start-ups hope to raise funds and for this, hurry to publish preliminary results to create maximum buzz and be able to finance the following stages. That’s the rule of the game…”.