Safety and immunogenicity of an optimized self-replicating RNA platform for low dose or single dose vaccine applications: a randomized, open label Phase I study in healthy volunteers.

Self-replicating RNA (srRNA) technology, in comparison to mRNA vaccines, has shown dose-sparing by approximately 10-fold and more durable immune responses. However, no improvements are observed in the adverse events profile. Here, we develop an srRNA vaccine platform with optimized non-coding regions and demonstrate immunogenicity and safety in preclinical and clinical development.

An internal ribosome entry site in the coding region of tyrosyl-DNA phosphodiesterase 2 drives alternative translation start.

Tyrosyl-DNA phosphodiesterase 2 (TDP2) is a multifunctional protein that has been implicated in a myriad of cellular pathways. Although most well-known for its phosphodiesterase activity removing stalled topoisomerase 2 from DNA, TDP2 has also been shown to interact with both survival and apoptotic mitogen-activated protein kinase (MAPK) signaling cascades. Moreover, it facilitates enterovirus replication and has been genetically linked to neurological disorders ranging from Parkinson's disease to dyslexia.

A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging.

Many genes that affect replicative lifespan (RLS) in the budding yeast Saccharomyces cerevisiae also affect aging in other organisms such as C. elegans and M. musculus.