Compact RNA sensors for increasingly complex functions of multiple inputs.

Autor:	Choe C; Department of Bioengineering, Stanford University School of Medicine, Stanford, CA, USA., Andreasson JOL; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.; Current address: Airity Technologies, Redwood City, CA, USA., Melaine F; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA., Kladwang W; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.; Current address: Inceptive, Palo Alto, CA, USA., Wu MJ; Program in Biomedical Informatics, Stanford University School of Medicine, Stanford, CA, USA.; Current address: Verily Life Sciences, South San Francisco, CA, USA., Portela F; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.; Eterna Massive Open Laboratory., Wellington-Oguri R; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.; Eterna Massive Open Laboratory., Nicol JJ; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.; Eterna Massive Open Laboratory., Wayment-Steele HK; Department of Chemistry, Stanford University, Stanford, CA, USA., Gotrik M; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.; Current address: Protillion Biosciences, Burlingame, CA, USA., Participants E; Eterna Massive Open Laboratory., Khatri P; Stanford Center for Biomedical Informatics Research, Stanford University, Stanford, CA, USA.; Stanford Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA., Greenleaf WJ; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Das R; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.; Program in Biomedical Informatics, Stanford University School of Medicine, Stanford, CA, USA.; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 16. Date of Electronic Publication: 2024 Jan 16.
DOI:	10.1101/2024.01.04.572289
Abstrakt:	Designing single molecules that compute general functions of input molecular partners represents a major unsolved challenge in molecular design. Here, we demonstrate that high-throughput, iterative experimental testing of diverse RNA designs crowdsourced from Eterna yields sensors of increasingly complex functions of input oligonucleotide concentrations. After designing single-input RNA sensors with activation ratios beyond our detection limits, we created logic gates, including challenging XOR and XNOR gates, and sensors that respond to the ratio of two inputs. Finally, we describe the OpenTB challenge, which elicited 85-nucleotide sensors that compute a score for diagnosing active tuberculosis, based on the ratio of products of three gene segments. Building on OpenTB design strategies, we created an algorithm Nucleologic that produces similarly compact sensors for the three-gene score based on RNA and DNA. These results open new avenues for diverse applications of compact, single molecule sensors previously limited by design complexity. Competing Interests: ETHICS DECLARATION The authors declare no competing interests.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu