Researchers closing in on genetic treatments for hereditary vision loss

Key Takeaways

  • Researchers have developed tiny drug carriers known as lipid nanoparticles that can deliver therapeutic genetic material to the eye.
  • The new lipid nanoparticles may overcome known limitations of using adeno-associated virus, the vehicle currently used to deliver gene therapy.

Researchers who work with tiny drug carriers known as lipid nanoparticles have developed a new type of material capable of reaching the eyes, an important step toward genetic therapy for inherited vision loss. Unlike other types of lipid nanoparticles that tend to accumulate in the liver, the ones in this study, based on the compound thiophene, can navigate their way to the retina, where they deliver their therapeutic payload. The researchers refer to these new lipids as Thio-lipids.

The researchers demonstrated, by using mice and non-human primates, the possibility of using Thio-lipids in lipid nanoparticles to deliver messenger RNA, the technology underpinning COVID-19 vaccines, to combat genetic blindness. Lipids are organic compounds containing fatty tails and are found in many natural oils and waxes, and nanoparticles are tiny pieces of material ranging in size from one- to 100-billionths of a meter. Messenger RNA delivers instructions to cells for making a particular protein.

With the coronavirus vaccines, the mRNA carried by the lipid nanoparticles instructs cells to make a harmless piece of the virus’ spike protein, which triggers an immune response from the body. As a therapy for vision impairment resulting from inherited retinal degeneration, the mRNA would instruct cells in the retina — which don’t work right because of a genetic mutation — to manufacture the proteins needed for sight. 

Thiophene-based lipid nanoparticles may provide a valuable alternative to the current primary means of delivery for gene editing: a type of virus known as adeno-associated virus, or AAV. “AAV has limited packaging capacity compared to lipid nanoparticles and it can prompt an immune system response,” said Gaurav Sahay, who co-led the study. “It also doesn’t do fantastically well in continuing to express the enzymes the editing tool uses as molecular scissors to make cuts in the DNA to be edited.”

Sahay calls the Thio-lipid findings “highly encouraging” but says more studies are needed, including research on the lipids’ long-term impact on retinal health. “But we think our results serve as a proof of concept and we will continue to explore Thio-lipids in potential treatments of…retinal genetic diseases,” he said.

Funding was provided by the National Eye Institute, the Oregon National Primate Research Center and the Casey Eye Institute. The results were published in the Proceedings of the National Academy of Sciences.

Source: Oregon State University, ScienceDaily, March 5, 2024; see source article