Scientists at Rice University and Baylor College of Medicine have created a new gene-editing method that dramatically increases the effectiveness of liver therapies. This technology, which boosts repaired cell rates from 1% to 25%, holds the potential to treat over 700 genetic liver disorders.
Researchers from Rice University and Baylor College of Medicine (BCM) have developed a new gene-editing strategy called Repair Drive, which significantly enhances the effectiveness of gene therapies in the liver. This advancement, described in a paper published in Science Translational Medicine, could pave the way for treatments addressing around 700 genetic disorders affecting the liver and potentially other organs and tissues.
Gene-editing therapies exist but are often hampered by high costs and the practice of breaking or inactivating defective genes rather than repairing them.
Repair Drive changes this narrative by repairing a higher percentage of liver cells — known as hepatocytes — effectively giving them an advantage to outcompete unedited and incorrectly edited cells.
“For example, homology directed repair is the preferred pathway for fixing genes, but it is only active in the roughly 1% of liver cells that are actively dividing. This limitation has made it nearly impossible to correct genetic mutations in a significant portion of the liver. Our approach is to take that small percentage of precisely repaired cells and give them a reason to divide so that they can replace the unhealthy liver cells,” co-senior author William Lagor, a professor of integrative physiology at BCM, said in a news release.
This new technique employs small interfering RNA (siRNA) to temporarily inhibit an essential gene, FAH, crucial for hepatocyte survival.
The researchers then introduced a modified version of FAH along with a therapeutic gene, allowing only gene-edited cells to survive and proliferate.
“This is like giving gene-edited cells a head start in a race,” added co-senior author Gang Bao, the A.J. Foyt Family Professor of Bioengineering at Rice.
Bao’s lab, which has been significantly advancing gene-editing research, conducted next-generation sequencing and bioinformatics analysis to ensure the precision of the gene edits performed with the new Repair Drive platform.
Bao highlighted the project’s collaborative nature and praised the key contributors. He lauded Marco De Giorgi, an assistant professor in the Lagor lab at BCM and the paper’s first author, for his “persistence and vision to overcome difficult biological and technical challenges.”
The significance of this research lies in its broader implications for genetic therapies.
“We’re not just focusing on one disease but instead offering a solution that could be applied to a broad range of conditions caused by genetic mutations in the liver,” Bao added.
The potential impact of Repair Drive is immense, offering a new avenue for restoring healthy liver cells and expanding the scope of treatable genetic disorders.