The exploration of potential treatment for Angelman syndrome by CRISPR-Cas9 system

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860955
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: LIU XIAOXI 国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (20709216)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: CRISPR/Cas9 / Angelman syndrome

Outline of Final Research Achievements

In this study we evaluated the potential of using CRISPR/Cas9 as a novel method to rescue the paternal imprinted UBE3A gene to rescue Angelman syndrome. We also examined how the sequence features of sgRNA correlate with the on-target activity. We found that nucleotides at both PAM-distal and PAM-proximal regions of the sgRNA are significantly correlated with on-target efficiency. Furthermore, we also demonstrated that the genomic context of the targeted DNA, the GC percentage, and the secondary structure of sgRNA are critical factors contributing to cleavage efficiency. In summary, our study reveals important parameters for the design of sgRNAs with high on-target efficiencies, especially in the context of high throughput applications.

Free Research Field

精神神経科学