Innovative RNA-Based Therapy Targets Mutant Genes in Children's Rapid Aging Disease

Children diagnosed with Hutchinson-Gilford Progeria Syndrome (HGPS), a rare genetic disorder causing accelerated aging, often exhibit symptoms like deep wrinkles, stunted growth, and brittle bones starting as early as 1 to 2 years old. This condition affects approximately one in eight million people and currently has no cure. The only FDA-approved medication, lonafarnib (Zokinvy), offers limited benefits, extending lifespan by about 2.5 years at a significant cost and with potential side effects.

Recently, a groundbreaking study led by Dr. Sun-Uk Kim at the Korea Research Institute of Bioscience and Biotechnology (KRIBB) has introduced a novel, precise RNA-targeting therapy that could revolutionize treatment for progeria. Published in the journal Molecular Therapy, this approach utilizes advanced gene regulation technology to selectively degrade the abnormal RNA transcripts responsible for producing progerin—an toxic protein that damages cell nuclei and speeds up cellular aging.

Unlike traditional gene editing techniques like CRISPR, which permanently alter DNA and carry off-target risks, this new RNA-based method offers a safer and reversible alternative. It employs an RNA-guided molecular 'scissor' based on RfxCas13d protein paired with a specifically designed guide RNA targeting progerin transcripts. This enables the selective removal of harmful RNA while leaving healthy gene transcripts intact.

In experiments with mouse models carrying the progeria mutation, the therapy successfully reversed several disease hallmarks, including hair loss, skin atrophy, spinal curvature, and decreased mobility. Treated mice also exhibited improved body weight, reproductive organ function, and enhanced heart and muscle health, resembling healthy controls. Interestingly, findings suggest that progerin accumulates naturally in aging human skin cells, and the therapy could delay certain aging signs in these cells.

Dr. Kim emphasized that this technology holds promise beyond progeria, potentially benefiting over 15% of genetic disorders caused by RNA misregulation. He envisions it becoming a versatile platform for treating age-related diseases, cancers, and neurodegenerative conditions.

This innovation signals a significant step forward in targeted genetic therapies, showcasing the potential of RNA-guided interventions to improve quality of life for patients with currently incurable diseases.

Source: https://medicalxpress.com/news/2025-07-rna-scissors-precisely-mutant-gene.html