A Vision for Gene Therapy

Breakthroughs on mice could someday benefit humans

Anne Worner (Flickr/wefi_official)
Anne Worner (Flickr/wefi_official)

In a recent breakthrough, researchers at the University of California, Irvine and Case Western Reserve University successfully corrected a gene mutation responsible for vision loss in mice. The gene editing techniques used in the experiment could eventually be used to cure blindness in humans, says Susie Suh, an MD-PhD student at Case Western who was part of the research team.

This news comes soon after Jennifer Doudna and Emannuelle Charpentier, who in 2012 discovered the gene editing system known as CRISPR, won this year’s Nobel Prize in Chemistry. CRISPR aims to fix the errant DNA sequences that cause genes to malfunction, thereby leading to illness or disease, so that the genes can produce healthy proteins instead.

The mice in this experiment had harmful mutations in a gene known as Rpe65. Therefore, their retinas were unable to detect light and color. In humans, a similar mutation is linked to an inherited eye disorder called Leber congenital amaurosis, which leads to severe vision loss in infancy and sometimes to complete blindness. Researchers used a refinement of the original CRISPR technique to fix the exact spots producing the problematic mutation in the DNA codes of mice.

This pinpoint approach, known as base editing, aims to reduce the risk that fixing one part of a gene inadvertently creates problems somewhere else. Five weeks after treatment, mice that underwent base editing to correct their vision could detect and react to light almost as well as mice with normal vision. Suh and colleagues are confident that these improvements will be permanent.

Given that people harbor a vast number of genetic mutations, there are potential challenges to correcting individual mutations one by one. “CRISPR and base editing are dependent on the type of mutation, so you are only targeting the patients who have that mutation,” says Hemant Khanna, an ophthalmologist at the University of Massachusetts Medical School. Khanna is leading efforts to develop “mini genes” that would restore some visual function lost due to many different gene mutations, another treatment currently being tested in mice, with human studies and treatment envisioned later. The goal is not a complete restoration of the ability to see, because the genes are miniature and not full-strength. In Khanna’s view, this sacrifice in potency is worth the gain of reaching more people than is possible with gene editing focused on a particular mutation.

As the painstaking work to bring gene editing to fruition continues, so does the debate over its ethics. Opponents of gene editing warn that it could lead to playing God, with proponents arguing that any strategy that could improve or even save people’s lives must be considered. However the field evolves, gene therapy for addressing eye disease, at least, is here to stay.


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Marcus A. Banks is a freelance journalist.


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