RNA Rescue challenge invites players to solve puzzles and advance RNA therapeutics

Researchers at UC Santa Cruz working to develop novel RNA-based medicines are teaming up with a new group of collaborators—players of the online game Eterna. The game’s new “OpenASO: RNA Rescue” challenge will tap into the collective intelligence of Eterna’s 250,000 registered users to help design an RNA drug for the treatment of hemophilia A.

“The Eterna player community may be able to come up with designs that we wouldn’t get using traditional screening methodologies for drug development,” said Michael Stone, professor of chemistry and biochemistry at UC Santa Cruz.

Eterna is an open science platform that has been engaging citizen scientists in RNA-related puzzles for over 10 years. Previous challenges have included OpenVaccine, to design a more stable mRNA vaccine against COVID-19, and OpenTB, to develop a new diagnostic device to detect tuberculosis.

UCSC researchers will synthesize the top ASO designs proposed by Eterna players and test them in laboratory experiments. The UCSC team includes Victor Tse (above), a graduate student in MCD Biology. (Photo by Sharif Ezzat/Eterna)

Stone and his colleagues at UCSC—including molecular biologist Jeremy Sanford and geneticist Olena Vaske, both faculty in the Department of Molecular, Cell and Developmental Biology—have been working to develop therapies for diseases caused by genetic mutations that disrupt the processing of RNA in the cell. One approach that has shown promise in treating this type of disease is called antisense oligonucleotide (ASO) therapy.

In all cells, RNA molecules copy information from DNA and direct the synthesis of proteins. ASOs are short segments of RNA designed to bind to specific cellular RNA molecules. They can modify gene expression or RNA processing and, in some cases, correct defects caused by genetic mutations. But developing an ASO that has the desired effect typically requires “brute force” screening efforts that can take many years to yield positive results.

“One of the goals of our project is to accelerate that discovery process,” Stone said. “That’s where Eterna comes in.”