Tokenizing DNA-Encoded Chemical Libraries with Non-Fungible Tokens (NFTs): A Scalable Framework for Registration, Provenance, and Transfer of Ultra-Large Small-Molecule Asset Collections

DNA-encoded chemical libraries (DECLs/DELs) enable the pooled synthesis and selection of millions to billions of DNA-barcoded small molecules, providing an efficient route to discover binders and early leads against diverse biological targets. As DEL-derived programs advance toward identifying clinical candidates, the asset surface of a DEL platform expands from a small set of optimized hits to include library designs, building-block combinations, DNA tags, selection data, and physical library stocks, thus creating new challenges in registration, traceability, and scalable ownership in transfer practices. Non-fungible tokens (NFTs) are unique blockchain-native tokens that can represent digital assets that can be coupled to smart contracts to enable traceable transactions and programmable rights management, which inspire proposals to tokenize intellectual-property (IP) assets such as patents. Here, we review (i) the scientific and commercial value of DEL in modern drug discovery, (ii) NFT/blockchain concepts, specifically in reported biomedical-IP and supply-chain use cases, and (iii) a conceptual architecture for NFT-enabled registration and controlled transfer of DEL libraries or sublibraries using on-chain identifiers with off-chain encrypted metadata and legal agreements.