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.
Open access
Chemical Synthesis and Analysis
Innovative Microfluidic and Catalytic Techniques Innovation
Anne M. Luescher, Andreas L. Gimpel, Wendelin J. Stark, Reinhard Heckel · 5 authors
Abstract Physical unclonable functions (PUFs) based on unique tokens generated by random manufacturing processes have been proposed as an alternative to mathematical one-way algorithms. However, these tokens are not distributable, which is a disadvantage for decentralized applications. Finding unclonable, yet distributable functions would help bridge this gap and expand the applications of object-bound cryptography. Here we show that large random DNA pools with a segmented structure of alternating constant and randomly generated portions are able to calculate distinct outputs from millions of inputs in a specific and reproducible manner, in analogy to physical unclonable functions. Our experimental data with pools comprising up to >10 10 unique sequences and encompassing >750 comparisons of resulting outputs demonstrate that the proposed chemical unclonable function (CUF) system is robust, distributable, and scalable. Based on this proof of concept, CUF-based anti-counterfeiting systems, non-fungible objects and decentralized multi-user authentication are conceivable.
Open access
DNA and Biological Computing
Physical Unclonable Functions (PUFs) and Hardware Security
Salmonella represents one of the major causes of foodborne diseases in humans, in addition to provoking important economic losses in the agri-food sector worldwide. Therefore, the surveillance and control of this human pathogenic bacterium in foodstuffs and biological fluids are necessary in order to prevent and diagnose the disease. Molecular methods based on the detection of DNA sequences specific to pathogenic species are an appealing alternative to traditional culture-based methods that require 5 to 6 days to obtain a definitive result. Among them, and because of its easy miniaturization, electrochemical genosensors are a suitable option for decentralized genetic testing [1-2]; however, they often require a set of sample pretreatment steps before genetic DNA analysis, thus making their implementation at the point of need more difficult. Herein, we report the integration of a nucleic acid-based sensor and an isothermal DNA amplification technique, helicase-dependent amplification or HDA, onto indium tin oxide (ITO) surfaces for the detection of a DNA sequence specific for the typA gene of Salmonella. DNA amplification process occurs at 65 ºC with short oligonucleotides flanking the target sequence, which act as primers. The reversed primer is covalently bound to the ITO surface through a thiol group present at its 5’ terminus, whereas forward fluorescein-tagged primer is incorporated in solution. As a result of the isothermal elongation step, fluorescein-tagged DNA duplexes are attached to the ITO surface and their enzymatic labelling is achieved via Fab fragments directed against fluorescein, conjugated with the redox enzyme alkaline phosphatase. Then, α-naphthyl phosphate is enzymatically dephosphorylated into an electroactive derivate α-naphthol whose amount, directly related to the Salmonella present in the sample, is measured by differential pulse voltammetry. This developed integrated sensing platform allows the detection of Salmonella down to 10 genomes in just over 2 hours [3], the same detection limit as that achieved by real-time PCR but without need of high-end benchtop instrumentation. Furthermore, the sensing layer built onto ITO surfaces maintains its performance even after 9 months storage, and possesses a great potential to be extended to the in-situ, fast and reliable detection of other pathogens. References: [1] D. Mabey, R.W. Peeling, A. Ustianowski and M.D. Perkins, Nat. Rev Microbiol., 2004, 2, 231-240. [2] A.S. Patterson, K. Hsieh, H.T. Soh and K.W. Plaxco, Trends Biotechnol., 2013, 31, 704-712. [3] S. Barreda-García, R. Miranda-Castro, N. de-los-Santos-Álvarez, A.J. Miranda-Ordieres, M.J. Lobo-Castañón, Chem. Comm., 2017, 53, 9721-9724. Acknowledgments: This work has been supported by the Spanish Ministerio de Economía y Competitividad (CTQ2015-63567-R), the Principado de Asturias government (FC-15-GRUPIN14-025), and co-financed by FEDER funds.