Will scientists be able to assemble a ribosome in vitro, composed entirely of synthetic proteins and RNA, without the use of cell-derived materials by 2030?
Started
Jul 01, 2025 04:00AM UTC
Closing Jul 01, 2026 04:00AM UTC
Closing Jul 01, 2026 04:00AM UTC
Ribosomes are complex molecular machines responsible for protein synthesis, consisting of two subunits (one small and one large subunit) that combine during protein synthesis (Molecular Biology of the Cell, National Human Genome Research Institute, Khan Academy). The subunits are both composed of ribosomal RNA (rRNA) and proteins.
A key step in the creation of mirror life would be the creation of a mirror-version ribosome. The creation of a mirror ribosome is unlikely to be feasible before protocols for the synthesis and assembly of 100% synthetic natural-chirality ribosomes is achieved.
To date, this has only been achieved for the small ribosomal subunit (30S). In 2020, scientists at the Weizmann Institute of Science achieved the autonomous synthesis and assembly of the small subunit of Escherichia coli (E. coli) outside a living cell by using synthetic genes to produce all necessary ribosomal proteins, RNA, and assembly factors (Science). The experiment was performed on a chip, which allowed the components to be synthesized and captured in close proximity, enabling them to self-assemble stepwise into functional ribosomal subunits (Phys.org, Weizmann Institute).
However, the large subunit is significantly more complex than the small subunit, as it is roughly twice the size of the small subunit and it contains a much larger rRNA component that forms the site for peptide bond formation. This rRNA also requires extensive post-translation modification to function, which is difficult to mimic via synthetic RNA synthesis. Thus, total synthesis and assembly of the large subunit, without the need for native ribosomal components from native cells, has yet to be achieved.
Resolution Criteria:
This is an unscored question that closes for forecasting on 1 July 2026. Although this is an unscored question, we outline the theoretical resolution criteria here.
This question will resolve as “Yes” if, by 31 December 2030, a peer-reviewed scientific publication or a scientific preprint reports the successful in vitro synthesis and assembly of a functional ribosome that meets all of the following criteria:
- Complete synthesis: All ribosomal proteins must be chemically synthesized or produced recombinantly, not extracted from natural cells. All ribosomal RNAs must be chemically synthesized or produced by in vitro transcription, not extracted from living cells.
- Self-assembly: The components are assembled in vitro in a fully defined chemical environment and do not contain any undefined cellular mixtures. For example, the use of crude or fractionated cell lysates or extracts (e.g. S30 or S15) would not qualify, but a reconstituted cell-free protein synthesis system (e.g. PUREfrex2.0) would qualify.
- Functional activity: The assembled 70S ribosome demonstrates measurable peptidyl transferase activity (the ability to catalyze peptide bond formation).
Partial assembly, assembly requiring natural cellular machinery, or assembly using components extracted from natural ribosomes will not qualify for a “Yes” resolution.