of Eterna as well as to provide series of pre-set puzzles for players to attempt. Player puzzles are generated by players, and Cloud Lab is where the active, proposed and archived laboratory projects are presented for players to review, vote or attempt. New players are guided through an initial puzzle progression which introduces the basic concepts of RNA structure and folding. As players proceed through puzzles of increasing complexity, the different game interface elements are described. After completing the 30 puzzles and earning all five Eterna Essentials badges, players gain access to the Cloud Lab where they can participate in laboratory research. Once players have completed a sufficient number of RNA puzzles, they unlock the chance to generate puzzles for other players. Biomedical challenges In 2016, Eterna launched its first biomedical challenge called OpenTB, an initiative to develop a new diagnostic device for tuberculosis. The project uses a gene expression "signature" discovered by Stanford researchers using public data, and aims to create an open source, paper-based diagnostic kit that can be easily deployed in clinics around the world. The development of the open source kit is a collaboration with MIT's Little Devices Lab. Players successfully designed RNAs to detect the gene signature by round 2 of the challenge, and as of February 2018 testing continues with real patient samples. Following the success of OpenTB, Eterna launched OpenCRISPR in August 2017, which challenges players to design single guide RNAs (sgRNAs) used in CRISPR gene editing. The goal of the project is to create a new class of sgRNAs that can be modulated by another small molecule (such as theophylline), allowing gene editing in the body to be turned on or off as needed. At the conclusion of round 1 in November 2017, players had submitted over 90,000 RNA designs for synthesis, the largest set of submissions to date. In response to the SARS-CoV-2 epidemic, Eterna joined the OpenVaccine collaboration to develop methods for stabilizing mRNA molecules that could be stored and shipped without the need for deep freezing. Players submitted 6000 designs for probing the stability of small RNA molecules at the nucleotide level, and used the results to design structured nanoluciferases that were tested for degradation in vitro and for protein expression in vivo. The OpenVaccine research resulted in novel methods and principles for designing stabilized mRNA therapeutics, including vaccines with potentially three times the current shelf life. Synthetic biology