Precision Medicine for Cystic Fibrosis and Vision Loss
Genetic disorders such as cystic fibrosis and inherited vision loss present significant challenges in the medical field, affecting thousands worldwide.
These conditions, caused by genetic mutations, lead to severe symptoms and a decreased quality of life for those affected. Addressing these disorders requires innovative treatment approaches that directly target and correct the underlying genetic errors.
In response, a collaborative research effort between Oregon State University College of Pharmacy and Oregon Health & Science University has led to a promising development. The team, led by Gaurav Sahay, Yulia Eygeris, and Renee Ryals, has focused on creating a new material that can precisely deliver genetic therapies to affected organs, specifically the lungs and eyes. Their findings, detailed in the Proceedings of the National Academy of Sciences, introduce a novel type of lipid nanoparticles.
These nanoparticles are based on a compound called thiophene, resulting in what the researchers have termed Thio-lipids. Unlike conventional lipid nanoparticles that predominantly collect in the liver, Thio-lipids have the unique ability to target lung and retinal tissues. This targeted delivery is crucial for effectively treating genetic conditions like cystic fibrosis, which impairs lung function and inherited retinal degenerations that lead to vision loss.
The research team has shown that Thio-lipids can encapsulate genetic medicines, including messenger RNA (mRNA) and CRISPR-Cas9 gene editors. This encapsulation is a critical step in delivering these therapies directly to the affected cells, offering the potential to treat and potentially cure rare genetic diseases. Yulia Eygeris highlighted the importance of the lipid's chemical structure in determining the nanoparticles' effectiveness and organ specificity.
The application of mRNA in lipid nanoparticles, a method popularised by its use in COVID-19 vaccines, shows great promise for genetic therapy. In this approach, mRNA instructs cells affected by genetic mutations to produce the necessary proteins, whether for lung function in cystic fibrosis patients or vision in those with inherited retinal degeneration. Cystic fibrosis, for example, is a condition marked by a defective CFTR gene, leading to lung infections and mucus build-up. It affects about 30,000 individuals in the U.S. alone, with around 1,000 new cases diagnosed annually.
The study's findings, derived from experiments with mice and non-human primates, signify a significant improvement over previous gene delivery methods, such as those using adeno-associated viruses (AAVs). AAVs have several limitations, including a restricted capacity and the potential to elicit an immune response, besides their reduced effectiveness in long-term gene expression.
While the initial results are promising, Gaurav Sahay acknowledges the need for further research to fully understand the long-term impact of Thio-lipids on retinal health. The work, supported by the contributions of other researchers from Oregon State University College of Pharmacy, including Mohit Gupta, Jeonghwan Kim, Antony Jozic, Milan Gautam, Jonas Renner, Dylan Nelson, and Elissa Bloom, represents a significant step forward in the quest to develop targeted treatments for genetic disorders. This research offers hope to those affected by such conditions and marks a milestone in the evolution of genetic therapies.
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Isabella Sterling
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