[3S00e] 01. ASBA - Part 9

4:50 PM - 5:05 PM JST(7:50 AM - 8:05 AM UTC)

[3ASBA-15] CRISPR beyond conventional editing

○Yu Wang¹ (1. Institute of Synthetic Biology, Shenzhen Institute of Advanced Sciences (China))

Keywords:

Nucleic Acids Therapeutics Development,RNA aptamer,CRISPR,Small Molecule

Nucleic acid therapeutics hold immense promise, but their broader clinical translation continues to be constrained by longstanding challenges in efficiency and precision. To overcome these barriers, an guide RNA-centered innovation framework grounded in fundamental molecular principles of CRISPR machinery was developed. First, guide RNA reengineering increased the precision of aptamer discovery by repurposing CRISPR as a molecular scaffold and enabling, for the first time, high-fidelity, function-driven aptamer screening directly in living cells. Second, RNA aptamer in silico generation improved the efficiency of aptamer evolution by integrating intracellular data with nucleic acid language models, thereby enabling the one-round generation of large numbers of candidates that surpass the best molecules obtained through conventional multi-round selection. Third, guide RNA regulation further enhanced the precision of CRISPR-based nucleic acid therapeutics by enabling tight control over the duration of editing activity, thereby allowing safer in situ targeting.