| Budget Amount *help |
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Outline of Final Research Achievements |
We have proposed a methodology to suppress the off-target effects of RNaseH-dependent antisense oligonucleotides by introducing chemical modifications optimized for nucleic acid-protein complex formation. We performed molecular dynamic simulations to extract structural features upon the RNasaH/DNA/RNA complex. Based on the simulated structures, we designed and synthesized chemical modification that restricts the position of complex formation. We confirmed the position of RNaseH complex formation was restricted upon the incorporation of chemical modifications. In addition, transcriptome analysis showed that the number of off-target genes was suppressed and the cell survival rate was improved. These results will contribute to the development of safer antisense oligonucleotides.
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