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Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA.

ABSTRACT: Lipid-like nanoparticles (LLNs) have shown great potential for RNA delivery. Lipid-like compounds are key components in LLNs. In this study, we investigated the effects of local structural transformation of lipid-like compounds on delivery of messenger RNA. Our results showed that position change of functional groups on lipid-like compounds can dramatically improve delivery efficiency. We then optimized formulation ratios of TNT-b10 LLNs, a lead material, increasing delivery efficiency over 2-fold. More importantly, pegylated TNT-b10 LLNs is stable for over four weeks and is over 10-fold more efficient than that of its counterpart TNT-a10 LLNs. Additionally, the optimal formulation O-TNT-b10 LLNs is capable of delivering mRNA encoding luciferase in vivo. These results provide useful insights into the design of next generation LLNs for mRNA delivery.

SUBMITTER: Li B

PROVIDER: S-EPMC4768262 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA.

Li Bin B Li Bin B Luo Xiao X Deng Binbin B Giancola JoLynn B JB McComb David W DW Schmittgen Thomas D TD Dong Yizhou Y

Scientific reports 20160226

Lipid-like nanoparticles (LLNs) have shown great potential for RNA delivery. Lipid-like compounds are key components in LLNs. In this study, we investigated the effects of local structural transformation of lipid-like compounds on delivery of messenger RNA. Our results showed that position change of functional groups on lipid-like compounds can dramatically improve delivery efficiency. We then optimized formulation ratios of TNT-b10 LLNs, a lead material, increasing delivery efficiency over 2-fo ...[more]

PMID: 26916931

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