ArticleMolecular therapy. Nucleic acids2025
A sort and sequence approach to dissect heterogeneity of response to a self-amplifying RNA vector in a novel human muscle cell line.
Article in Molecular therapy. Nucleic acids, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- SPRY domains encode ubiquitin ligase specificity for ZAP and RIG-I.PLoS pathogens · 2026Article
- Systems vaccinology analysis of saRNA immunization identifies an acute innate immune signature correlated with adaptive immunity.Molecular therapy. Advances · 2026Article
- Immunology of RNA-based vaccines: The critical interplay between inflammation and expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
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Authors and funding
7 authors.
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Abstract
Self-amplifying RNA (saRNA) is an extremely promising platform because it can produce more protein for less RNA. We used a sort and sequence approach to identify host cell factors associated with transgene expression from saRNA; the hypothesis was that cells with different expression levels would have different transcriptomes. We tested this in CDK4/hTERT immortalized human muscle cells transfected with Venezuelan equine encephalitis virus (VEEV)-derived saRNA encoding GFP. Cells with the highest expression levels had very high levels of transgene mRNA (5%-10% total reads); the cells sorted with low and negative levels of GFP protein also had detectable levels of both VEEV and GFP RNA. To understand host responses, we performed RNA sequencing. Differentially expressed gene (DEG) patterns varied with GFP expression; GFP high cells had many more DEGs, which were associated with protein synthesis and cell metabolism. Comparing profiles by an unsupervised approach revealed that negative cells expressed higher levels of cell-intrinsic immunity genes such as
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