Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery in vivo

Zhang, Tian; Yin, Han; Li, Yu; Yang, Haiyin; Ge, Kun; Zhang, Jinchao; Yuan, Qing; Dai, Xuyan; Naeem, Abid; Weng, Yuhua; Huang, Yuanyu; Liang, Xing-Jie

doi:10.1016/j.isci.2024.109804

iScience

2024

DOI: 10.1016/j.isci.2024.109804

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Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery in vivo

Tian Zhang,

Han Yin,

Yu Li

et al.

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1mΨ influences the performance of various positive-stranded RNA virus-based replicons

Miyazato,

Noguchi,

Ogawa

et al. 2024

Sci Rep

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Self-amplifying RNAs (saRNAs) are versatile vaccine platforms that take advantage of a viral RNA-dependent RNA polymerase (RdRp) to amplify the messenger RNA (mRNA) of an antigen of interest encoded within the backbone of the viral genome once inside the target cell. In recent years, more saRNA vaccines have been clinically tested with the hope of reducing the vaccination dose compared to the conventional mRNA approach. The use of N1-methyl-pseudouridine (1mΨ), which enhances RNA stability and reduces the innate immune response triggered by RNAs, is among the improvements included in the current mRNA vaccines. In the present study, we evaluated the effects of this modified nucleoside on various saRNA platforms based on different viruses. The results showed that different stages of the replication process were affected depending on the backbone virus. For TNCL, an insect virus of the Alphanodavirus genus, replication was impaired by poor recognition of viral RNA by RdRp. In contrast, the translation step was severely abrogated in coxsackievirus B3 (CVB3), a member of the Picornaviridae family. Finally, the effects of 1mΨ on Semliki forest virus (SFV), were not detrimental in in vitro studies, but no advantages were observed when immunogenicity was tested in vivo.

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1mΨ influences the performance of various positive-stranded RNA virus-based replicons

Miyazato,

Noguchi,

Ogawa

et al. 2024

Sci Rep

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show abstract

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Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery in vivo

Cited by 1 publication

References 143 publications

1mΨ influences the performance of various positive-stranded RNA virus-based replicons

1mΨ influences the performance of various positive-stranded RNA virus-based replicons

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