Modified self-amplifying RNA mediates robust and prolonged gene expression in the mouse and ex vivo human brain

Modified hm5C self-amplifying RNA enables over five weeks of sustained gene expression in mouse brain cells and more than 76 days in human brain slices.

• Why it matters: Effective, non-integrating gene delivery methods are needed for rapid and long-lasting protein expression in the brain to advance neuroscience research and therapies.
• What they did: Researchers developed and tested a modified 5-hydroxymethylcytidine saRNA encapsulated in LNPs, delivering fluorescent proteins into mouse brains and human cortical slices, with expression detectable from 24 hours to months.
• The result: This approach significantly outperforms traditional mRNA, enabling prolonged gene expression and retrograde labeling of neurons, opening new avenues for neuroscience and therapeutic applications.