Summary
A bioRxiv preprint describes RNA-fragment end joining (REJ), a modular system that joins separate RNA units into functional coding mRNAs. The reported platform supports gene complementation, intersectional cell labeling and expression of large proteins.
Researchers have described an RNA-based platform that joins separate RNA fragments into a functional coding messenger RNA. Called RNA-fragment end joining, or REJ, the system is designed for gene complementation and other applications that require selective expression of proteins inside cells.
The work appears as a bioRxiv preprint posted on September 14, 2026. In the abstract, the authors report demonstrations involving genetic complementation, intersectional labeling of cell types and expression of large proteins. These are research-stage platform applications rather than clinical results.
How REJ assembles a functional RNA message
Gene complementation involves supplying a functional gene product to restore or study a biological activity. It is also used in genetic selection and in experiments that test the function of proteins or genetic variants.
REJ approaches this by dividing a coding sequence between separate RNA units and using short, structured RNA modules of about 250 base pairs to bring the units together. The authors describe four functions for these modules:
- promoting interaction between the separate RNA molecules;
- recruiting the cell’s native splicing machinery to perform RNA trans-splicing, in which sequences from separate RNA molecules are joined;
- reducing translation from RNA segments that have not yet been joined; and
- encoding the protein without an added joining sequence, which the authors describe as scar-free protein expression.
Together, these features are intended to favour production of the complete coding message while limiting the formation of unintended protein fragments from the individual RNA units. The researchers report that REJ can reliably split nearly any gene into complementary segments, regardless of the structure of the protein it encodes.
Reported uses of the platform
The platform’s gene-complementation use could allow researchers to express complementary portions of a gene and assess whether the resulting joined message restores the intended protein function. The preprint also describes intersectional expression. In this experimental context, intersectional labeling generally means restricting a marker to cells where selected biological or cell-type conditions overlap, providing more precise control than a single expression signal.
The authors provide a collection of reporter tools and a web-based design tool intended to help researchers plan REJ vectors. Reported applications also include efficient expression of large proteins, an area where splitting the coding sequence into complementary units may be useful for experimental delivery and expression designs.
The supplied abstract does not give numerical efficiency measurements, sample sizes or details of the experimental models used for these demonstrations. The evidence available here therefore supports the introduction and stated applications of a molecular biology platform, while its performance across particular genes, cell types and delivery systems will depend on the detailed experiments.
The preprint discloses that the Salk Institute holds two patents covering REJ technology and that both have been licensed to Insmed. It also identifies several authors as inventors, with one author employed by Insmed and another serving as a consultant.