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DNA delivery using lipid nanoparticles results in severe toxicity in mice. However, we find that the incorporation of endogenous anti-inflammatory lipids into the lipid nanoparticles mitigates this toxicity and enables prolonged gene expression.
The mechanism of translation initiation in linear and circular mRNAs influences translation efficiency. Covalent attachment of an N7-methylguanosine (m7G) cap increases protein production from circular mRNAs in mice. Hybridization with capped endogenous RNAs also promotes protein production in cells, suggesting that this interaction might also occur between endogenous RNAs.
Visualizing RNA molecules in live cells remains a challenge, and existing methods require genetic manipulation or have limited resolution. Our study overcomes these limitations by using the programmable CRISPR–Csm tool to bind and track individual transcripts in their native state.
Society, patients and clinicians welcome a much-needed non-opioid pain medication. Vertex’s first-in-class analgesic Journavx could soon be followed by a new generation of addiction-free pain drugs acting at NaV1.8 sodium channels.
