Objective:

To investigate the role of microRNA-106a in reactivating the silenced MECP2 gene on the X chromosome in mouse models of Rett syndrome.

Approach:

• CRISPR-Cas9 Screening: The study performed a genome-wide CRISPR-Cas9 screen in female mouse fibroblasts to identify microRNAs involved in maintaining X chromosome inactivation.
• Gene Therapy: Researchers delivered an adeno-associated virus (AAV9) carrying a miR106a-targeting 'sponge' into the brains of female mice with heterozygous Mecp2 mutations.

Key Findings:

• Inhibition of miR106a restored MECP2 expression to about 32% of normal levels.
• Treated mice showed significant improvements in locomotion, exploratory behavior, and brain volume.
• Median survival of treated mice was 29.6 weeks compared to 12.1 weeks for controls.

Interpretation:

Limitations:

• The study was conducted in mouse models, and results may not directly translate to humans.
• Further research is needed to assess long-term effects and safety of the treatment.

Conclusion:

Sources:

• Nature Communications