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Related Concept Videos

mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
Nucleic Acid Structure01:25

Nucleic Acid Structure

The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms  a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA has a double-helix structure. The...

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Related Experiment Video

Updated: Jun 19, 2026

Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
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Fluorinated Lipid Nanoparticles for Enhancing mRNA Delivery Efficiency.

Huipeng Zhang1,2, Chaoyang Meng3, Xuewen Yi3

  • 1National Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

ACS Nano
|March 7, 2024
PubMed
Summary

Fluorinated modification of lipid nanoparticles (LNPs) enhances messenger RNA (mRNA) delivery and expression. This novel FPD modification improves cellular uptake and endosome escape, boosting therapeutic potential with favorable safety.

Keywords:
drug deliveryfluorinated PEG-lipidslipid nanoparticleslysosome escapemRNA deliveryprotein expression

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Area of Science:

  • Biotechnology
  • Nanomedicine
  • Drug Delivery

Background:

  • Lipid nanoparticles (LNPs) are promising nonviral vectors for nucleic acid delivery, crucial for vaccine and therapeutic applications.
  • Current LNPs face limitations in endosome escape efficiency and biosafety, hindering messenger RNA (mRNA) delivery efficacy.
  • Improving LNP performance is essential for maximizing the therapeutic potential of mRNA-based treatments.

Purpose of the Study:

  • To investigate the impact of fluorinated modification of PEG-DSPE (FPD) on LNP-mediated mRNA delivery.
  • To evaluate the efficiency of FPD-modified LNPs in enhancing cellular uptake and endosome escape.
  • To assess the in vivo efficacy and biosafety of FPD-modified LNPs for mRNA delivery.

Main Methods:

  • Synthesis and characterization of fluorinated lipid nanoparticles (FPD-LNPs).
  • In vitro assessment of mRNA expression in B16F10 tumor cells and primary dendritic cells.
  • In vivo evaluation of mRNA expression via intravenous and intraperitoneal injection in animal models.
  • Analysis of LNP cellular internalization and endosome escape mechanisms.

Main Results:

  • FPD-modified LNPs demonstrated a 5-fold and 2-fold increase in mRNA expression in tumor cells and dendritic cells, respectively.
  • In vivo studies showed at least a 3-fold augmentation in overall mRNA expression compared to non-fluorinated LNPs.
  • FPD introduction led to increased mRNA expression in the spleen compared to commercial DMG-PEG formulations.
  • Fluorinated LNPs exhibited favorable biosafety profiles at both cellular and organismal levels.

Conclusions:

  • Fluorinated modification of PEG-DSPE (FPD) significantly enhances LNP-mediated mRNA delivery efficiency and expression.
  • FPD promotes cellular internalization and endosome escape, addressing key limitations of current LNP technology.
  • The developed fluorinated LNPs offer improved in vivo efficacy and maintain a favorable safety profile, advancing mRNA-based therapeutics.