(433h) DNA Storage, Encryption, and Encoded Library: From Molecular Data Storage to New Drug Discovery

DNA-based data storage and encryption hold multiple advantages including ultra-high storage density, long-term stability and durability, low energy consumption, environmental friendliness, and enhanced data security. With continuous technological advancements and expanding applications, DNA storage and encryption are expected to replace existing data storage media, emerging as a crucial development direction in future data storage[1]. As a branch of DNA-mediated retrievable information storage, DNA-encoded chemical libraries (DELs) represent one of the earliest developed and most practical applications in DNA information storage. This technology features direct DNA-encoded tagging of chemical compounds, which can be considered a specialized case of molecular-scale chemical information read-write operations in DNA storage[2]. While the former belongs to information science, the latter integrates closely with pharmaceutical chemistry, and their convergence may inspire new advancements from molecular storage to drug discovery.

We have introduced cutting-edge nucleic acid research progress in DNA storage and encryption into DEL technology, integrating automated solutions such as digital microfluidics to develop a next-generation chip-based DNA-encoded library system - DEL-on-a-chip. We successfully constructed multiple novel molecular libraries featuring new scaffold structures and warheads, including natural product-derived steroid libraries and sulfonyl fluoride covalent libraries. Empowered by the DEL-on-a-chip technology, we identified several promising lead compounds with good activity against various drug targets such as PGAM1, HIF-1α, and PD-L1, demonstrating potential clinical translation value[3-4].

Concurrently, we discovered that frontier developments in DEL technology can reciprocally promote practical applications of DNA information storage. For instance, we adapted the long-established Headpiece technology from DEL systems to DNA data storage, significantly enhancing data storage stability, reliability, and anti-interference capabilities[5].

[1] Zhang, Y; Qu, Z.-b.; Pradeep Narayanan, R.; Williams, D.; et al., J. Am. Chem. Soc., 2021, 143: 8639.

[2] L Jiang, S Liu, X Jia, Q Gong, et al., J. Am. Chem. Soc., 2023, 145: 25283.

[3] Xue Z., Li H., Xie W., Xu Y et al., ACS Med. Chem. Lett. 2022, 13: 1864.

[4] Yang J., Lu Y., Hu K., Zhang X., Act. Pharmaceut. Sin. B. 2025, 15: 392.

[5] C Hu, Q Wen, Q Lai, Z Xie, et al., Chem. Commun. 2025, 61: 881.