Like most websites The Ophthalmologist uses cookies. In order to deliver a personalized, responsive service and to improve the site, we remember and store information about how you use it. Learn more.
Subspecialties Basic & Translational Research, Retina

From Darkness

Introducing a personalized antisense gene therapy for inherited retinal diseases

After decades of study into inherited retinal diseases (IRD), researchers at the Scheie Eye Institute at the University of Pennsylvania have tested  an antisense gene therapy-based approach for the treatment of Leber congenital amaurosis (LCA) caused by a specific mutation in the ciliopathy gene centrosomal protein 290 – CEP290 (1).  The intravitreal injection was developed by ProQR Therapeutics.

“LCA is the most severe form of IRD and thus has the greatest treatment potential,” says Artur Cideciyan, who led the clinical trial at the Scheie Eye Institute. “We were cautiously optimistic that successful pre-clinical experiments performed in the lab would translate into positive results in patients.” And the cautious optimism was justified: majority of the patients who  took part in the multi-center study experienced an improvement in visual acuity within the first three months  – with no serious adverse events. And one responder improved from barely being able to perceive light to 20/400.

Patients received intravitreal injections of a short RNA molecule designed to counter the mutation. Cideciyan explains in more detail: “The most common mutation in the CEP290 gene is a single nucleotide change in intron 26, which results in the introduction of aberrant exon and reduces the amount of CEP290 protein.” The oligonucleotide essentially blocks recognition of the aberrant exon, boosting the amount of non-mutant CEP290 protein in photoreceptors.

“We are in an era of personalized medicines and this is especially true for monogenic conditions, such as IRD. Many of the treatment avenues currently considered are specific to the gene involved – such as gene augmentation for recessive loss of function, or gene knockdown and replacement for dominant gain of function conditions,” explains Cideciyan. “Our current work takes this gene-specific personalized medicine for IRDs one step further by making the intervention mutation specific.”

Naturally, patients with different molecular mechanisms of the disease cannot benefit from such specific treatment, but does the research hold wider promise? According to Cideciyan: yes. “Our study showed for the first time that intravitreally injected oligonucleotides can modulate splicing in human photoreceptor cells and result in positive changes in vision. This work opens the door to evaluating similar approaches in other inherited retinal diseases.”

Enjoy our FREE content!

Log in or register to read this article in full and gain access to The Ophthalmologist’s entire content archive. It’s FREE and always will be!

Login if you already created an account

Or register now - it’s free and always will be!

You will benefit from:

  • Unlimited access to ALL articles
  • News, interviews & opinions from leading industry experts
  • Receive print (and PDF) copies of The Ophthalmologist magazine

Or Login as a Guest or via Social Media

  1. 1. AV Cideciyan et al., “Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect”, Nat Med [Epub ahead of print] (2019). PMID: 30559420

About the Author

Phoebe Harkin

I’ve always loved telling stories. So much so, I decided to make a job of it. I finished a Masters in Magazine Journalism and spent three years working as a creative copywriter before itchy feet sent me (back)packing. It took seven months and 13 countries, but I’m now happily settled on The Ophthalmologist, where I’m busy getting stuck into all things eyeballs.


Send me the latest from The Ophthalmologist.

Sign up now

Related Articles

Subspecialties Basic & Translational Research

Three (Hundred) Blind Mice

| Phoebe Harkin

Subspecialties Glaucoma

A Glimpse Over the Horizon

| Jeffrey O'Callaghan

Subspecialties Cataract

The Crystal Maze

| Eugene Serebryany, Phoebe Harkin

Most Popular

Register to The Ophthalmologist

Register to access our FREE online portfolio, request the magazine in print and manage your preferences.

You will benefit from:

  • Unlimited access to ALL articles
  • News, interviews & opinions from leading industry experts
  • Receive print (and PDF) copies of The Ophthalmologist magazine